Larry Gopnik, a physics professor at a quiet mid-western university has been informed by his wife Judith that she is leaving him. She has fallen in love with one of his more pompous colleagues, Sy Ableman. Larry's unemployable brother Arthur is sleeping on the couch, his son Danny is a discipline problem, and his daughter Sarah is filching money from his wallet in order to save up for a nose job. Just when you thought things can't get any worse, an anonymous hostile letter-writer is trying to sabotage Larry's chances for tenure at the university. Also, a graduate student seems to be trying to bribe him for a passing grade while at the same time threatening to sue him for defamation. Plus, the beautiful woman next door torments him by sunbathing nude. Struggling for equilibrium, Larry seeks advice from three different rabbis.