First off, I'd like to say "Hello :3". Lolz. Ok, so I'm assuming you were expecting a fail build on Twitch like many of the others spammed here or want to laugh since I said serious guide. Well, I am being serious and very detailed in this guide. Many think it is easy commanding Twitch, but the are false. He does, like every champion, require both skill and brains to use. I can't give you the skills required to play Twitch, but I can guide you to the brains (Zombies FTW <3). I bet most of you are just dying to laugh at this guide due to the fact that most people believe Twitch is OP and just takes a click to play, but I've seen my share of horrible Twitch playing Summoners that wasted their 6k IP since they failed so nasty with Twitch, they never played him again. So, shove that laughter past your thong and into your butt until you actually finish reading this guide fully. Especially that Twitch is so squishy that he makes the mushrooms on Super Mario Bros. not look squishy...AT ALL. Ok, I couldn't think of anything else to say (>.>), but Twitch is very squishy and that is huge downside, because a few deaths at start can ruin his whole game.

I purchased Twitch the moment I got 6k IP and played him in almost every game until, the last few months, I've played multiple characters due to boredom of him. Well, my last game (as of writing this), I said to myself "Hell, I want to try out on-hit effects" and did so. The worst part is that the opponents, magically, were premade in a solo queue 5v5 and targeted me so nasty that I died 10 times before reaching level 15. I wasn't careless, it was just so crazy on how much they cared more about me dying than anyone else. Even 2 champions (Kass & Shaco) always carried oracle and placed multiple wards for their team. Anyhow, once I had this "on-hit effect" build up to Madred's, I was massacring every single champion on the opponents team. I know you may be thinking that this is stupid and doesn't dish out as much of damage as a full on physical Twitch, but from what I experienced in that game was so outrageous that I had to change my guide to it. I can shred through tanks, squishes, super minions, and towers with no problem.

Other Builds
Good:
- Full on DPS damage.
- Fast movement speed.
- High criticals.

Bad:
- Very high gold cost.
- Low attack speed.
- Can be difficult to take out tanks.
- Can be countered by Armor.
- Very squishy.
- Very dependent on ganking/stealth.
- Very dependent on criticals with Infinity Edge.
- Must get Frozen Mallet or Banshee's Veil for health if targeted too much.

My build
Good:
- Low gold cost (Compared to other builds.)
- Both Magic and DPS damage.
- Higher survivability.
- Your build will make others think you are a horrible Twitch.
- Your opponents will be confused on how you are dishing out so much damage.
- Armor won't have much effect on your damage output.
- Your opponent will run out of mana very quickly.
- Can kill both tanks and squishes.

Bad:
- Hybrid/Not 1 damage type output.
- Average movement speed.

If I missed something, please let me know.

I honestly have never read any Lore, but I thought I'd put this here for those die hard fans and make this guide a bit more serious. Definitely, not to make this guide look longer. *Cough*

The city-state of Zaun is a twisted realm of science, mercantilism, and magic run amok. While the young science of techmaturgy does much to advance civilization, its research and use in Zaun pushes the boundaries of morality on a daily basis. Zaun, choked with pollution from the countless factories and laboratories that spew waste into the environment, suffers greatly. As polluted as Zaun is above-ground, its subterranean levels are far worse. All of Zaun's runoff waste pooled together in its sewers, mixing into a toxic and mysterious concoction. A single plague rat rose from this alchemical nightmare - Twitch. Unlike his lesser evolved cousins, Twitch became as sentient as anyone else... provided they were as insane as he. A seeming byproduct of the evolutionary brew that spawned him was maniacal insanity, albeit in a functional form.

Twitch came to the League of Legends to represent himself ''as the only one of his kind'' on the Fields of Justice. Since then, he has found a generous benefactor in the city that gave him his evolutionary sentience - Zaun. Twitch is one of Zaun's premier champions in the League, and as such he fights for Zaun when political disputes between Valoran's city-states arise. Twitch has publically stated that his goal is to gain enough influence and materiel from his work in the League to try to recreate the process by which he gained his sentience. While many challenges lie ahead in his quest - one of the largest being his own insanity - were he to succeed, it would mean a bold and brazen step forward in the evolution of all of Runeterra. Zaun has pledged its support for Twitch in his quest, though it remains to be seen what Zaun's ulterior motives are in the matter.

''The existence of Twitch proves that anything is possible on Runeterra.''
-- Heimerdinger

Quote is from Riot's League of Legends: http://www.leagueoflegends.com/champions/29/twitch_the_plague_rat

I'll get to this as soon as possible. I'm just not fully done with this build due to some crazy ideas that I've come up with that work nicely.

Twitch's masteries are simply DPS cliche. Always have 21 in Offense and 9 in the other 2 trees (depending on what tree you prefer). If you have less than 21 in the Offense, then you are obviously playing twitch wrong since he isn't an effective tank and ability power isn't his strong suit or you just are under level 21...lolz.

However you may notice a few things odd, compared to other builds, in my masteries:

1) I take a point in Cripple to increase my normal damage and Expunge using it's armor/magic resist reduction. I honestly don't see anything useful in putting 1 point in Archmage's Savvy or Plentiful Bounty . Since your Expunge is at it's best early and mid game, then the small ability per level is a waste and Smite on a Twitch is not effective at all.

2) I put two points in Burning Embers (to increase the damage output on Expunge which does actually make a difference early and mid game) and two more points in Alacrity (increases attack speed which honestly can give you a tiny advantage in a 1v1 in very early game) instead of 3 points in Brute Force , because 3 attack damage (from Brute Force) really is nothing compared to 2% more attack speed and +10 Ability Power (when Ignite is on cooldown).

3) I chose to put 9 points in Defense instead of Utility (for the experience, health/mana regen, and 1 gold per 10 seconds), because I'd prefer to not allow Twitch to be too squishy and up his survivability a bit. He gains 4 magic resist, 4 armor, 2% Dodge chance, and a possible 10% boost in movement speed in which in my opinion is better. He doesn't need health/mana regeneration and if you are thinking that he needs more mana regeneration, then you are playing him wrong, because I have never ran into a moment in which I needed more mana. If it happens to you often, then get the blue buff from the opponents' side. Some of you may also be thinking that Twitch needs the 5% experience increase to gain an advantage, but with all his kills, it is pretty pointless since he reaches 18 rather quickly and I haven't ever noticed a difference when I had the points in those masteries than when I didn't. Lastly, the gold per 10 seconds is a joke. If you ask "why?", then I hope god has mercy on your soul. Lolz...

Ignite
I believe this is a wonderful combo with your poison and Expunge. I tend to sometimes overestimate my Expunge and that middle laner gets away with 1-10 hp, but never lives when I choose ignite. Also, with the mastery in Burning Embers you can increase the damage of your Expunge when Ignite is on cooldown. Ignite is also a wonderful counter against champions who rely on health regeneration or life steal. For example: Sion's Cannibalism, Dr. Mundo's Maximum Dosage, Fiddlesticks' Bountiful Harvest, Tryndamere's Undying Rage (most Tryn's stay attacking for about 3-5 seconds before running away with 1-100 HP), and few more champions I can't remember at the moment.

Exhaust
Also, you may think that Exhaust is a stupid spell to get since Twitch can already slow with his ability, but Exhaust is meant to be used at start of game to kill that middle laner in order to gain advantage and some easy gold. Besides the slow increase, it also can give you that damage increase with the mastery penetration boost. So, including your 20 armor penetration with your runes you also gain another 10 with a nice estimate of 30 which is true damage on most champions at early game. Oh, it also has a wonderful add-on effect that disables a DPS champion for a few seconds. Blind. Talk about early game survivability for Twitch.

Revive
I know most of you may be thinking that revive is for noobs, but I could care less. Instead of getting pissed over those damn people who have about 100hp or less left over after you died, you bust this out and BAM! Also, the bonus health that the mastery (if you choose to put it) gives is very nice for even more survivability. If you normally die about 5 or less times, then every one of those deaths, you could be respawning right back into action to save the game from a huge turnover. Wonderful late game spell.

Flash
I don't like Flash because I honestly suck at using it...end of story...haha. I do really hate Flash as my summoner spell as I see it useless for a small jump (unless in jungle) due to the one fact that you character stops walking its path when this is used. So, he loses out on a 0.5-2 sec walk (depending on how quick you are) in which the enemy could probably catch up or get in range...that is just my opinion as I've killed many running Ezreals who have Flash even when I don't. Speed > Flash and with this build, a PD, boots, exhaust, & Pray N' Spray out run any Flash.

Cleanse
I would only recommend this in a Ranked game since they usually use Exhaust or many CC moves on you and once Twitch gets disabled, it is game and you will no longer be a carry, but instead rat meat.

Teleport
Some people love teleport for the sneaky ganks using a ward in a bush or whatever, but with the phantom dancers and Revive's speed boost, I can get there in just the same amount of time, basically and I get to revive on death which surprises the enemy greatly by thinking that they finally killed me.

Sword of the Divine
This is an excellent item for Twitch, because of the active it has. "Your attacks cannot be dodged and you gain 30 Armor Penetration for 8 seconds." This absolutely destroys anyone trying to blind you with Exhaust and removes 30 Armor penetration which is just crazy awesome. Also, 8 seconds is way longer than Exhaust and plenty of time to mow anyone down with Twitch. I honestly have no idea why I have never tried this item, but I sure am now going to.

Infinity Edge
This item should be on every Twitch or ranged DPS character as it gives them everything they need. Never get more than one. You do and you are just a pure noob. The reason it costs so much is that the Unique Passive is crazy good, but doesn't stack (EVER) since it is "UNIQUE PASSIVE". Why am I pushing this hard? Well, I've seen people do it and they fail horribly since they are wasting their gold and sacrificing Attack Speed.

Phantom Dancer
This item is another one of Twitch's core items because it give him what every Twitch needs. It raises his Attack Speed (max is 2.5), Critical Chance to go with your Infinity Edge, and lastly give you a nice boost of speed to ensure your kills. You can get it before or after Infinity Edge, it is up to you, but my preference is after.

The Bloodthirster
If the game isn't over yet, then the only other option is getting two Bloodthirsters, because it improves your survivability greatly (to stop you from losing the match since respawn by this time takes too long) and increases your damage nicely.

Tiamat
Wonderful with those enemies that bunch up like bunches of oats on the battlefield. This is an awesome combo with your ult. This item is basically is giving you extra damage if your enemies are near each other. [Edit: I honestly don't see it worth the price due to the patch where all ranged champions were nurfed.]

Malady
You may be thinking that this guide was written before the patch that changed this, but no and I am fully aware that this a hardcore magical item. So, why get this item? Well, Twitch's only magical damage ability is only wonderful at start. Yes, his Expunge. It increases your attack speed and removes magic resist based on stacks (Champions don't have much in early game). This also makes your enemy think "wtf? this Twitch is a noob." and thus get them aggressive and cocky which increases your chances of a kill. So, I only recommend you get this as your first item after the dagger and sell it later. Trust me, this rare to see on a Twitch, only because it is a pro item for him at start.

Wit's End
This will kill most of the enemies' mana which basically disables them in team fights. very effective with his attack speed, but I don't use it often. You can also use this as a nice mid game items if you are laning mid, because without mana, your opponent can't do anything, but hold out at turret until it is safe for him to recall.

Guinsoo's Rageblade
I've seen many people who get away with about 100 or less HP, but with this item, it will increase your Expunge, thus making sure they die. This is very effective against Tryn as he won't expect a random nuke of magic out of Twitch. Believe me, I see a lot of people forget about his Expunge and with this item it gives Twitch everything he needs (Speed & Attack Damage) plus a huge damage increase to his Expunge.

The Black Cleaver
First of all I'd recommend this over the Last Whisper for many reason. If they have less than 150, then this is better than the Last Whisper. Especially with Twitch's fast attack speed which allows you to gain quick stacks in order to shred those tanks easily. Note: It takes 2 seconds to get those five stacks since the highest you can get is 2.5 attack speed. [Math: 100-25(from runes)=75-45(3 stacks)=30]

Last Whisper
If they stack more than 150, then this is what you need since 40% can go a long way when they have a lot of armor in which is usually only great against Rammus and Malphite. Note: Flat penetration is usually better than percentage, because percentage is applied after flat penetration which makes a huge difference. [Math: 100-25(from runes)=75-40%=45 Armor]

Frozen Mallet
I only recommend this item, because the slow on hit effect is just magical on Twitch for those runners and makes you feel like you stole Ashe's Frost Shot but without using any mana. Anyhow, If you are always being targeted and die before you can really do anything, then would be a must get item for you glass summoners.

Madred's Bloodrazor
I see these a lot on Twitch, but I honestly think that if you get this item, then you lack the attack damage Twitch should have. By getting this item, you spoil the point in getting Bloodthirster, making your armor pen less effective, and letting down your critical damage with Infinity Edge. Also, if they have Magic Resist, then say goodbye to the damage. Some love it, but I just don't find it as effective as more attack damage even though Twitch has nice Attack Speed.

TRY TO BECOME A GREAT MID LANER!!!
Mid is perfect for Twitch as long as you don't die more than once. Being mid gives you that edge of surprise on ganks (since they can't really call MIAs on a Twitch), being a higher level, etc. If you aren't a great mid laner, then, team up with Nasus, Nunu & Willump, or any stun/snare/slow champion like Sion, Morgana, Lux, and Taric. Nasus' Wither and Spirit Fire works magic. Nunu & Willump's Ice Blast and Blood Boil does wonders. Some team up with Warwick for the huge attack speed increase from Hunters Call, but to be honest, Warwick should be jungling and Twitch has enough attack speed once he gets Sword of the Divine.

I think this is also a great spot to input the two big questions many people ask when playing as Twitch.

1) "What if they have Vision Wards?"
Twitch may be scared of wards, but wards are his best friend also. Just buy a damn Vision Ward, place it in order to see their wards, destroy the wards, and make sure they don't destroy your Vision Wards to see if they have any. It is as simple as that. Counter their Vision Wards with Oracle's Elixir or another Vision Ward. I find Oracle's Elixir less cost effective than a Vision Wards, because it sets back your build a bit.

2) "What if they have Oracle's Elixir?"
Another simple solution. Gank from the bush like any other champion would. If you are against a Teemo in the mid lane, then ask your buddies to come gank him (make sure they aren't dumb enough to set off the mushroom's either. If your buddies are too busy or just hate your guts for crying for mid, then you have two options. One, pretend you don't notice their oracle (trust me...it sadly works) and get as close as possible to Teemo while looking stupid by hovering near them sneakily. Then jump out of Ambush and use Exhaust + Venom Cask + Ignite and blow your ultimate (it has wonderful range). Once he starts to run and exhaust is running out or you notice he is getting out of range, bust your Expunge. Dead animal meat is what you have in seconds. If he doesn't run, DO NOT be too afraid of near death experiences. As long as you have 3 bars when you bust Expunge (with 6 stacks due your ultimate), he is dead before you are and the left over poison will leave you barely alive. Then you...RUN LIKE HELL!!!

Now that we have that covered, let's move on...

Early Game (1-5):

Just try to stay alive, last hit minions, harass, and not do anything stupid. You know, the usual. Also, if you know that you are strong enough, try to pick off a few kills in mid lane or with your partner.

Mid Game (6-10):

This is the most important part of playing as Twitch and shows everyone if you are great or not. You have to play sneaky and smart during this time. Turret dive using Expunge and Ignite combo after busting your ult on them and gaining 6 stacks in no time. Always make sure to check the bushes for any surprise gankers and for any Vision Wards or champions with Oracle's Elixir. Not doing these 3 things are the biggest mistakes any summoner playing Twitch can make.

Mid-Late Game (11-16):

If you are not already carrying the team and/or backdoored nasty with your Sword of the Divine + Berserker's Greaves + Infinity Edge, then you need to! Twitch is one of the best backdooring champions due to his attack speed, damage, and invisibility. He should also be the shining star of the game with a high kill/death ratio once it has reached this point of the game.

Late Game (6-16):

If you end up lasting longer than 30-45 minutes, then stack 2 Bloodthirsters and initiate on the champions since you will gain so much health back faster than the damage received.

I came across an old detailed guide and this guy couldn't say it any better:

Gank Style Combat:

When you go to attack them, your teammate should be in front of them, if there is room for you to get behind them or to their sides at least at 300-500 range (NOT MAX RANGE, as they could use this oppurtunity to run the opposite direction possibly) Now is when you initiate the fight, get as many shots off, ONCE THEY NOTICE AND START REACTING TO YOUR ATTACK pop debilitating poison, which is more than enough slow, to get your poison up to 6 stacks, and time for your teammate to move in, and then just blow expunge with 6 stacks on and watch them drop dead.

Team Style Combat:

Fighting in team battles is actually a lot like your gank scenarios except now, you are bringing target priority back into the game, and positioning becomes a lot more important than gank style combat. In team fights, if you have aoe slows and stuns consider using spray and pray to pump out some good aoe damage, otherwise if you dont have them, stick to regular attacks. (Knowing when and when not to use Spray and Pray is extremely important, i can't stress this enough because of how many twitches i've fought that will jump me and pop Spray and Pray and i literally just walk back and forth dodging them or by using hit and run's (as a ranged hero) on him without any retialiation because of spray and prays shots) Usually as far as positioning goes you want to try and stay towards the outer edges of the combat (sort of like a flanking position but more towards your team, dont ever isolate yourself from your team.

Quote and credits belong to this guy: http://www.leagueoflegends.com/board/showthread.php?t=12537

Umm...hi? Eh, I mean bye? Come on man give me a break. I have never been good with closing or ending anything. Well, guess I'll try anyhow.

As you can see it takes quite a bit of time to get the skills and brains to use Twitch properly and not some dead rat meat waiting to get eating. As I've said in the intro, he is VERY squishy which causes many players to give up in trying him again. I hope this extensive guide to using Twitch helps anyone in using him or gets you hungry to spend 6k IP (or a few $$$...lolzercopter...) in order to play this awesome guy! Trust me, he doesn't smell that bad. Ok, fine I'll stop with the lame jokes now...

Good Luck & Have Fun!