Reign Over Me stars Adam Sandler in a non-comedic role. He plays Charlie Fineman, who from all appearances appears to suffer from a mental disorder. Charlie is seen by a former college buddy of his as he zips along the street on a motorized skateboard. His friend calls out to him, but Charlie is oblivious to his calls. His college friend, who is named Alan, jumps in his car and pursues Charlie down the street. Eventually, Alan catches up with Charlie and gets him to recognize who he is. Alan is married and a successful dentist, and he wonders what Charlie has been up to all these years.
Alan and Charlie start spending time together, and Alan quickly learns there is something disturbing about the way Charlie lives. Charlie lives in a spacious apartment, where he is perpetually in the state of redecorating the kitchen. Charlie's personality is detached and aloof and he often accuses Alan of being "one of them." Despite misgivings by his wife, Alan continues to spend time with Charlie in an attempt to get him to open up about the tragedy which took place in his life.
Charlie had a wife and three daughters who all died when the twin towers were hit on 9/11. After the tragic event, Charlie began to withdraw inside himself and refused to discuss anything related to his wife and children. This causes a lot of concern for Charlie's in-laws, who love him and want to see him lead a normal life. Alan thinks he can help Charlie by getting him to see a therapist who works in his building. Charlie seems to respond to his friendship with Alan and does agree to see the therapist.
Over the course of several visits, Charlie still remains distant when it comes to talking about his family. One day, while he and Alan are sitting in the waiting area, he begins to talk about the beautiful wife and daughters he had and how much he loved them. Ultimately, what brings Charlie back to life is the power of the friendship he has with Alan.