Lazy stoner Dale Denton (Seth Rogen) purchases a rare new strain of weed called Pineapple Express from his dealer, Saul Silver (James Franco). However, when Dale witnesses a murder committed by a crooked cop (Rosie Perez) and the city's most dangerous drug lord (Gary Cole), he panics and dumps the weed at the scene. He discovers that the weed is so rare that it can be traced back to him and the bad guys are on the hunt to kill them both.