Andrew Largeman (Zach Braff) is a semi-successful television actor who plays a retarded quarterback. His somewhat controlling and psychiatrist father has led Andrew ("Large") to believe that his mother's wheelchair bound life was his fault. Andrew decides to lay off the drugs that his father and his doctor made him believe that he needed, and he begins to see life for what it is. He begins to feel the pain he had longed for, and begins to have a genuine relationship with a girl who has some problems of her own (Natalie Portman).
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