A young street magician is left to take care of his little sister after his mother's passing and turns to drug dealing in the Los Angeles party scene to keep a roof over their heads. When he gets into trouble with his supplier, his sister is kidnapped and he is forced to rely on both his sleight of hand and brilliant mind to save her.

Samantha MacKenzie, the daughter of the president of the United States, arrives at college with a group of Secret Service agents. Samantha, however, resents their presence and decides she wants to attend school just like a normal student. Her father agrees to recall the agents but secretly assigns James, an undercover agent, to pose as a student. They fall in love, but their romance is jeopardized when Samantha learns James' true identity.

The series follows the ventures of a Missing Persons Unit of the FBI in New York City.

In the unreal world of Sacred Heart Hospital, John "J.D." Dorian learns the ways of medicine, friendship and life.