This is my first guide iv done so don't be to harsh. This is MY way of doing twitch... Twitch is, as most people realize, a very finesse champion. So in order to use this guide effectively you need to have some common sense on how he works. I have been told before and I find this to be very true... "You cannot teach common sense." So that being said here it goes...

Please try to read this guide all the way through before you comment, some of the odd choices make more since after you read it fully.

Pros
-Huge nuke from level 2 and threw end game
-Stealth for MIA scares and harassment
-Can solo mid quite easily
-Can score multi-kills easy with ulti.
-Very strong late game (One of the best carries IMO)
-Awesome BD champ!

Cons
-VERY squishy (Cannot info-size this enough)
-Weakened A LOT by Oracle's Extract or wards (These should be on the top of your list to eliminate)

I personally use this set up since it covers the majority of what your gonna run into. Some use the Greater Quintessence of Fortitude, but honestly for me personally, I find the seal health build up to be much more effective long game. The Armor pen runes will drastically boost your damage (Crits end game being over 1k). I started off using attack speed marks, this was a waste of marks on twitch... With his item selection, and stealth maxed, he hits 2.5 attack speed easy.

Kinda self explanatory... The only things I wish to explain that very from most the builds I see is the spell focus masteries. I use ignite after the initial fight (at level 1) to harass the lane (since you can use this spell and not break stealth) and the extra 10 spell power (since its always on CD when I attack) adds that little extra damage to your nuke (Expunge). I also took Exhaustion mastery point since I saw the spell point as a waste.

Twitch is all about dealing damage quick and getting the **** out of there. If you sit in a 1v1 fight for more than 3-5 seconds (against a good player) you will be dead. The goal of this mastery set up is to optimize your damage output as fast as possible.

These are... IMO the perfect nuking set. Now all equipment is adjustable due to situations, and play style. That being said... If I am having a great blow out game, I do lose one of the Blood Thurster's for Sword of the Occult. If I am being cc'ed a lot I pick up a Cloak and Dagger instead of a phantom dancer. And if the Cloak and Dagger arent enough I pick up a Quicksilver Sash, but I rarely see the need for both. On occasion, you will fight health build champions, the best item against them is Madred's Bloodrazor. Feel free to change these as need to fit your play style or the game, 85% crit, 2.5 attack speed and 1k crits... with plenty of life leach to keep you up in almost all scenarios, this is my nuke set choices.

I personally do my skills in this order to get the largest nuke early in the game. I rarely have champions get away from me after I start an attack (So i don't get the slow maxed until late in game) If they do start to get away from me I always have a exhaust handy for this situation. Also I find that 1 rank in the slow is enough to get the kills off until later in the game when you need to slow the whole team for team fights (offensively or defensively)

I used to use Flash and Ignite, but recently, I went to Exhaust instead since it has more usefulness in late game for me. But this is again based on play style. Another useful spell is Ghost, as chasing some down is difficult, and could be the difference between a kill and them slipping away.

Twitch is very strong in team fights. This is where he shines... With his ulti hitting multiple targets, the enemy team can b nuked down quickly. He works well with coordinated ganks, preferred if he does not lead them off though.

All-in-all, he is one of the best team fight characters.

Another benefit to twitch's ulti is if you sit on a turret hidden as the other team runs in to attack it, after they stack up on it, this makes for a great way to line everyone up easily and get you a few multi kills.

I stick to mid lane early game, this gives you the advantage in not only level, but you can easily go MIA and help your bot and top lanes with stealth. When used correctly, the enemy team will never see you coming due to all the MIA's you can do just by going stealth to harass your mid opponent.

Late in the game, when everyone is team fighting (Roughly about 20 minutes) when everyone start to gravitate to middle. If you are in need of cash, head to the outer lanes and kill the larger groups of creeps, don't be afraid to use your ulti to nuke them down quickly and rejoin the team fights in middle.

With all the advantages twitch has, he has a lot of disadvantages too. The trick is to get early kills and carry your self to the top as soon as possible. Once you get your Infinity Edge, its game on for hunting... Don't be afraid to sneak around and get the ganks you most defiantly need to finish him. His flaws are easily covered with a little bit of thinking and planning on all your attacks.

I hope you enjoyed this "Guide" on twitch, another tip I'll add in that some down realize on Twitch is that if you hit your stealth before recall (before you go stealth hit recall {B}) you will be hidden for your recall. I find this to be handy more than a few times.

I hope you have enjoyed this guide, I haven't been playing LoL but about a month. In this time, I have learned a lot about the game and the research you need to put into each champion before you play it. This being said, I hope it helps someone else out.