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Leonard Shelby (Guy Pearce) remembers everything up to the night his wife was brutally raped and murdered. But since that tragedy, he has suffered from short-term memory loss and cannot recall any event, the places he has visited or anyone he has met just minutes before.
Determined to find out why his wife was killed, the only way he can store evidence is on scraps of paper, by taking Polaroid photos and tattooing vital clues on his body.
Throughout his investigation, he appears to have the help of both bartender Natalie (Carrie-Ann Moss), who may have her own secret agenda and police officer Teddy (Joe Pantoliano) whose friendship is always suspect.
As Shelby's fractured memory tries to piece together a chilling jigsaw of deceit and betrayal in reverse, breathtaking twists and surprising turns rapidly occur in the most challenging, original and critically acclaimed thriller in years.