Als dem dauerbekifften Dale mitten in der Nacht der Stoff ausgeht, macht er sich auf den Weg zu seinem Dealer Saul. Der hat was ganz Besonderes für ihn parat: eine Neuzüchtung namens „Ananas Express“. Doch ehe Dale in den Genuss kommt, wird er zufällig Zeuge eines Mafia-Mordes, in den eine korrupte Polizistin und der städtische Drogenboss verwickelt sind. Bei seiner panischen Flucht lässt er dummerweise einen Joint mit Ananas Express am Tatort zurück, was ihn und seinen Dealer ganz oben auf die Abschussliste der Gangster bringt. Auf der wilden Flucht vor dem Mob wird den beiden Kiffern schnell klar, dass sie nicht an Gras-bedingter Paranoia leiden, sondern wahrlich Grund zur Sorge um ihr Leben haben…

Several lost-soul night-owls, including a nightclub owner, a talkback radio relationships counseller, and an itinerant stranger have encounters that expose their contradictions and anxieties about love and acceptance.

Nick Pearson is a life-long bachelor who is finally settling down. On the brink of his wedding he is surprised to find he has a 13 year old son who has come to find his him through the help of a psychic. The problem is Nick can't stand kids and would happily send the boy back to live with his biological mother, except that no one has any clue who that might be. Having nowhere to turn Nick must hit the road with the boy and the neurotic, inept psychic to track down dozens of his disgraced ex-flings to whom he must ask the awkward question - with very mixed results.

A divorced doctor finds himself in real trouble living with his daughter alone now. But fortunately a guardian angel is watching over the lives of both of them.