Anytime...

Claire Howell shows up in an episode, yell "bitch!" then take a drink.

A gratuitous act of violence is shown onscreen, drink and say, "Cable shot! It's not TV, it's HBO."

One of the really femmy gay guys actually speaks, drink two.

A character on the show swears at and/or threatens their family member (e.g. "Fuck everything you believe in," "Quit your fuckin' whining," "Fuck you Aunt Brenda," etc), drink.

One of the Wiseguys starts waxing nostalgic about the past or reciting old Sicilian folklore, down a shot of Sambuca.

When anyone has sex, take a drink. Chug if it's a member of the opposite sex. (Only take two drinks if it's McManus and a female staff member.)

During any self-gratification scenes, sing the chorus to Billy Idol's "Dancing With Myself," then down your drink.

Your favorite charcter is either thrown into the hole or is shown in the shower, buy a round for the house, reach into your wallet and immediately cough up a check to HBO for another years subscription.

Throughout any scenes that CO Hughes is in, take that much-needed moment to go pee.