The film follows the story of former college roommates and old friends Alan and Charlie, the latter of whom is struggling with depression after the death of his wife and daughters in the September 11 attacks.

Five years have passed since Charlie's wife and daughters died, and now the once-successful and sociable man has become a withdrawn shadow of his former self.

Charlie approaches his in-laws in the lobby of the courthouse, stating that he does not carry pictures nor discuss his family because he sees them every day, in the faces of people walking down the street.

The site's critical consensus reads, "Reign Over Me is a charming, affecting tale of friendship and loss, with solid performances from Adam Sandler as a broken, grief-stricken man and Don Cheadle as his old friend and savior.

"[2] On Metacritic, the film has a weighted average score of 61 out of 100, based on 33 critics, indicating "generally favorable reviews".

[3] Audiences surveyed by CinemaScore gave the film a grade A− on scale of A to F.[4][5] Lisa Schwarzbaum at Entertainment Weekly gave Reign Over Me a B− rating, calling the film "a strange, black-and-blue therapeutic drama equally mottled with likable good intentions and agitating clumsiness."

She shared her own discomfort with seeing the September 11 attacks casually included as a plot device in a fictional dramedy, though praised the film's performances and story.

"[8] In an interview with Vogue Magazine in 2017, when a reporter asked British actress Daisy Ridley her a question of the film that makes her cry the most, her response was "Reign Over Me with Adam Sandler".