Drink every time someone says that they're going to be the Pirate King. Drink twice if it's not Luffy.
Sip every time anyone screams. Do not try this alone.
Hard mode: Sip only when a scream is held for more than five seconds. The result won't be much different.
Drink every time Zoro gets lost.
Two if they're still rather close to one of his crewmates.
Drink whenever someone explains their power. Drink twice if it's in the middle of the battle.
Drink if someone does something physically impossible with their powers.
Drink at every Michael Jackson/zombie movie reference you can find during Thriller Bark.
Drink every time they make a joke about Luffy and meat. That includes hungry jokes, manic eating, "I want food", and the like.
Drink at every new Devil Fruit the show introduces.
Drink every time a named character doesn't die when they should have (powerful attacks, No One Could Survive That, stuff). Drink twice if someone actually dies.
If ever a part of the song Binkusu No Sake is sung, pause the episode/chapter, pour a full glass, find the song and do your best to sing along while taking a swig every so often. If you still have some left when it's done, drain the glass.
Drink every time the strawhats fight amongst each other. Drink again if it's not Zoro and Sanji who are fighting.
Hard Mode: Drink every time the straw hats fight amongst each other, and it is NOT Played for Laughs.
Drink every time someone says nakama. Dub notwithstanding.
Drink every time someone has a demon head and yells at someone else for doing/saying something stupid. Drink twice if it's not Nami.
Pour a full glass and drink the whole thing every time a character mows down a huge bunch of enemies. Do only half a glass if it's Luffy mowing them down. This could save your life when you get to the Enies Lobby arc.
Drink every time Brook jokes about not having the body part he just referred to and laughs afterwards
Drink every time Brook asks to see someone's panties.
Drink every time Ace acts like a Wangst or makes crying/choking noises during Marineford.