Detectives Marcus Burnett and Mike Lowrey of the Miami Narcotics Task Force are tasked with stopping the flow of the drug Ecstasy into Miami. They track the drugs to the whacked-out Cuban drug lord Johnny Tapia, who is also involved in a bloody war with Russian and Haitian mobsters. If that isn't bad enough, there's tension between the two detectives when Marcus discovers that playboy Mike is secretly romancing Marcus’ sister, Syd.

Marcus Burnett is a henpecked family man. Mike Lowrey is a footloose and fancy free ladies' man. Both Miami policemen, they have 72 hours to reclaim a consignment of drugs stolen from under their station's nose. To complicate matters, in order to get the assistance of the sole witness to a murder, they have to pretend to be each other.