New York psychiatrist Dr. Nathan Conrad (MICHAEL DOUGLAS) lives the good life on the Upper West Side with his beautiful wife, Aggie (FAMKE JANSSEN), and their 8-year-old daughter, Jessie (SKYE McCOLE BARTUSIAK). Although he's now considered uptown, that doesn't prevent his former colleague, Dr. Louis Sachs (OLIVER PLATT), from calling him in for a special case on the night before Thanksgiving.
It seems that Sachs' newest patient, Elisabeth Burrows (BRITTANY MURPHY), is a very troubled young woman who's now locked up after attacking an orderly. With a history of misdiagnoses and multiple hospitalizations, no one has been able to crack Elisabeth's case and Louis is worried that if he and Nathan can't do so soon, the girl will be sent away forever.
Nathan agrees to do what he can, but soon learns that others are interested in Elisabeth, but for different reasons. Waking up Thanksgiving morning, Nathan and Aggie - who's bedridden with a broken leg - discover that Jessie has been kidnapped. It seems that Patrick Koster (SEAN BEAN) and his group of thugs have abducted the girl and threaten to kill her if Nathan can't extract a specific six-digit number from Elisabeth's tangled psyche that will help them retrieve a valuable jewel they stole a decade earlier.
With a 5 o'clock deadline and instructions not to contact the police since the kidnappers will be watching his and Aggie's every move, Nathan sets out to do what he can. As NYPD detective Sandra Cassidy (JENNIFER ESPOSITO) follows the trail of a homicide that eventually leads her toward the kidnappers, and Jessie tries to befriend some of them, such as Max (CONRAD GOODE), Nathan races against the clock as he tries everything possible to get Elisabeth to give up the number.