Leonard Shelby is tracking down the man who raped and murdered his wife. The difficulty of locating his wife's killer, however, is compounded by the fact that he suffers from a rare, untreatable form of short-term memory loss. Although he can recall details of life before his accident, Leonard cannot remember what happened fifteen minutes ago, where he's going, or why.

Police sergeant Neil Howie is called to an island village in search of a missing girl whom the locals claim never existed. Stranger still, however, are the rituals that take place there.