This build works with Alcrity runes and will not have anywhere near the same effect with Desolation. If you have Desolation runes check out the other builds with AD early game; this build is based on attack speed, then damage. Not damage then attack speed. Please take this into account before you comment. Give this build a few goes before you rate.

I have spent some more time playing with the ability list and I am inclined to agree with some of the comments that Debilitating Poison is need a little bit earlier. So its now at level 5.

Also I have changed the Item list, scrapping Vampiric Sceptre for Doran's Blade.

Hey, I've been playing Twitch for a while now and he is by far my favourite champion. If your a smart enough player you can do marvellous things with this hero. Twitch is a fairly easy character to get to grips with abilities wise. They aren't complicated but they are devastating. The difficult bit comes with placement. Where you fight with this hero and how you do it can affect you greatly, it can turn you spanking into them ganking. I'll hopefully be able to explain more of this if you read on!

My rune choice for this build is based on the fantastic rune guide by Searz.

The armour penetration is for that extra damage against all enemies and even better when facing someone with a bit more health, or armour.

The attack speed is a must, early game it can give you significant advantage because you'll be able to put a lot more poison on a target which means your expunge will deal more damage as they run. Combined with your ambush you can have a mad attack speed at level 1; magic.

The mana regeneration is fairly self explanatory. Twitches expunge is great but uses a lot of mana, this should keep you in the lane for longer early game.

Finally, magic resistance is just to give you that bit more defense against enemies. If your playing mid you can guarantee that the opposing champion will have some sort of spell use, this will keep you in the fray.

The masteries are pretty open for interpretation once you've filled offence. Twitches damage doesn't come from his abilities mid to late game, its from his bow damage. The rest of the mastery points I've spread out across the trees, those are my choices.

First item you have a few choices, either Doran's Blade or Vampiric Sceptre. If you think your great take the Sceptre. If you do take the Blade make sure to sell it around mid game and get the Sceptre ready for Bloodthirster, you won't need that 100 health or 10 damage by that point, your Infinity Edge will be more than enough.

Twitches damage comes from his speed in this build as well as his critical and his attack damage. By starting with Zeal and Berserker Boots your attack speed along with masteries and runes is pretty amazing, once you've got those you can build the Phantom Dancer which will give you great critical hit damage and attack speed. As a bonus these items are relatively cheap so you can get them quickly; also combined with the boots you get 430 run speed which is great for setting up ganks.

Once your speed is sorted out, you could use some attack damage; some critical hit chance would be nice too. Fortunately Infinity Edge solves those problems, it will add massive damage and make your critical hits ridonkulous. Considering by late game you'll be at 70 to 80 critical hit chance it is a massive damage boost that will catch everyone off guard.

After infinity edge you can make 2 choices, make these choices based on the opposing team. You can go into you Bloodthirster and rack up some mad damage and then some lifesteal too, however if they have a heavy armour team then get the Black Cleaver first as it will shred their armour for you and for your team.

If its a very long game take another Phantom Dancer to boost your critical hit chance to the ridiculous, and if you make that then sell your boots for another Bloodthirster of if they are heavy health team take Madred's Bloodrazor, you won't need the boots any more as two dancers will keep your run speed near enough the same as it was before.

I use Clarity and Exhaust, clarity is a must early game as your expunge will sap your mana if you are making a lot of kill attempts. Also exhaust as its one of the most useful spells, in order to take down high DPS enemies such as Yi. If you don't fancy Clarity then Ignite can help you to get those early kills if applied correctly.

Ambush
Ambush is your main ability, you will use this a hell of a lot. Its not only for stealth its for your attack speed too, a big boost to boot. You should be using this ability a lot, its great because it inspires a lot of fear and makes enemies play a bit more defensively. You can run around the back and open up a new one for you foes. Remember though that the duration of the speed buff is longer if you have stealthed for longer. If you run in to gank then apply it a few seconds before hand to make sure it lasts the fight. You should also use this when running into new minion mobs if your farming, just to speed up the process.
N.B. Clarity and Heal will cancel this ability.

Debilitating Poison
This move is great when you've got a few attacks in and they start to peg it, slap it on and then get a few more attacks in and just as they think they are away, Expunge their face off!

Expunge
This is your finishing move. Once you've done your damage and got your poisons on and slowed them so you've dealt your damage then Expunge their face off! Again...
Pay attention to is range, you can leave them to run for a while as the poisons take more health, then make the finish! Don't use on minions as this is a waste of mana and you'll find yourself in the summoners circle more than the lane.

Spray and Pray
This move is the bomb, it fires arrows through all opponents at great range, get your placement right so you can get more champions, after 1 or 2 hits Debilitating Poison them and slap more shots on, then Expunge their face off! One more time...
With such small cool down you can use it for runners, solos and in team fights. Don't be afraid to use it lots! Be liberal with this move! Go nuts!

Twitch is a great champion for ganking, if your comfortable with your team you can work together to set up ganks early game, only if your team is competent. Leaving a lane to get a gank might seem good but if it fails then you've wasted time, farming money and experience by wandering off. Wait till you get your Phantom Dancer and Berserker Boots so you can run around a bit faster.

Early game you want to try and pick your foes 1v1. get behind them if they are away from your turret and open up if not harass with your base attack, don't waste Expunge to get health down if it won't kill, its a lot of mana to waste. Wait until they have poisons on them and as they run and Expunge.

Mid to late game you can start to pick team fights up with your Spray and Pray; it is your friend and with a short cool down its a move you can afford to use even if it doesn't get you a kill. Making them run off to their base to recharge is still time in the field you've gained.

Ambush should be used liberally, and before you get near minions. If they don't know your there, you have free reign to set yourself up and think about your fight plan. If you are going to loose a tower and they are going to team tower dive on it, pop up and Spray and Pray. Mega damage and they won't expect it, make sure you hug the tower though. You won't get a kill from it, but it buys time.

Your attack speed early game will also make farming very easy, just open up Ambush in a group of minions and leave it on auto attack. Don't be afraid to pick up neutral monster buffs, by level 7 you can easily solo them; remember though if you die, you've just handed it to them.

Let me know if have missed something I can adjust/change it.

Be gentle...