John Murdoch (Rufus Sewell) awakens alone in a strange hotel to find he is wanted for a series of brutal murders. His memories have vanished and even his beautiful wife, Emma (Jennifer Connelly) has become estranged from him. So begins a quest to unravel the mysteries of his past; a quest tat will take him into a fiendish underworld where he is relentlessly pursued by the police and a group of shadow-like beings known as the Strangers and where only the sinister Doctor Schreber (Keifer Sutherland) is able to help him...