A coming of age tale that focuses on brothers Arty and Jay, left in the care of their Grandma Kurnitz and Aunt Bella in Yonkers, New York. Their desperate father, Eddie, works as a traveling salesman to pay off debts incurred following the death of his wife. Grandma is a severe, frightfully intimidating immigrant who terrified her children as they were growing up, damaging each of them to varying degrees. Bella is a sweet but mentally slow and highly excitable woman who longs to marry an usher at the local movie house so she can escape the oppressive household and create a life and family of her own. Her brother Louie is a small-time, tough-talking hoodlum who is on the run, while her sister Gert suffers from a breathing problem with causes more psychological than physical problems. Missing much of the sentimentality of the plays comprising Simon's earlier Eugene trilogy, Lost in Yonkers climaxes with a dramatic confrontation between embittered mother and lonely daughter that creates a permanent fissure in this highly dysfunctional family.