It is 1967, and Larry Gopnik, a physics professor at a quiet Midwestern university, has just been informed by his wife Judith that she is leaving him. She has fallen in love with one of his more pompous acquaintances Sy Ableman.

A man takes matters into his own hands when a pharmaceutical kingpin moves into his town to cause some real trouble.

For decades, next-door neighbors and former friends John and Max have feuded, trading insults and wicked pranks. When an attractive widow moves in nearby, their bad blood erupts into a high-stakes rivalry full of naughty jokes and adolescent hijinks.