Plot
Novelist Larry Donner struggles with writer's block due to his resentment towards his ex-wife Margaret, who took all the credit for his manuscript and received acclaim for it, while Larry, struggling to make ends meet, takes a job teaching creative writing at a community college. Owen Lift is a timid, middle-aged man who still lives with his overbearing, harsh and paranoid mother. Owen’s mother is more paranoid when she fears that Owen would get someone to take her away to a retirement home. Owen fantasizes about killing his mother but can't summon the courage to bring his desires to fruition.
As a student in Larry's class, Owen is given advice by Larry to view an Alfred Hitchcock film to gain some insight into plot development for his murder stories. He sees Strangers on a Train , in which two strangers conspire to commit a murder for each other, figuring their lack of connection to the victim will, in theory, establish a perfect alibi. Having overheard Larry's public rant that he wished his ex-wife dead, Owen forms a plan to kill Margaret, believing that Larry will, in return, kill his mother.
Owen tracks Margaret to Hawaii and follows her onto a cruise ship she is taking to her book signing, where he plans to push her overboard. He returns from Hawaii to tell Larry of Margaret's death and that he now "owes" him the murder of his mother, lest he inform the police that Larry was the killer.
After having spent the night drinking alone on a beach during the hours of Margaret's disappearance, Larry panics because he lacks a sufficient alibi. That, along with a news report announcing that the police suspect foul play, convinces Larry that he's the prime suspect.
Larry goes to stay with Owen and his mother in an attempt to hide from the police. He meets Mrs. Lift, but despite her harsh treatment of him he refuses to kill her. Eventually, when she drives Owen to the breaking point, Larry finally relents and agrees to go through with the murder.
After two unsuccessful attempts, Larry flees the Lift home when Mrs. Lift recognizes him as a suspect from a news broadcast about his ex-wife's disappearance. He boards a train to Mexico and Owen and Mrs. Lift come along so as to avoid having to lie for him. During the journey, Larry's patience with Mrs. Lift finally runs out when she impolitely gives him advice on writing.
Larry follows her to the caboose with the intent of killing her, but Owen begins having second thoughts about having her killed and gives chase. In the ensuing struggle, Mrs. Lift hangs from the train, but is rescued by Owen and a repentant Larry. She is grateful to her son for saving her, but unappreciative of Larry's help and kicks him, resulting in him losing his balance and falling off the train to the tracks below.
During his recovery in the hospital, Larry discovers that Margaret is still alive; she had fallen overboard accidentally and was rescued by a Polynesian fisherman whom she has decided to marry. Much to his annoyance, Larry learns that Margaret plans to sell the rights of her ordeal for $1.5 million. On the advice of a fellow patient, Larry chooses to free himself of his obsession with his ex-wife and instead focus on his own life, and write about what recently happened to him, thereby freeing him of his writer's block.
A year later, Larry has finished a novel based on his experiences with Owen and Mrs. Lift, titled Throw Momma from the Train. Owen visits and informs him that his mother has died (albeit naturally) and that he's going to New York City for the release of his own book. Owen reveals that his book is also about their experiences together.
Thinking that his book has been scooped once again, an enraged Larry proceeds to strangle him, but stops when Owen shows him that his book is a children's pop-up book called Momma, and Owen, and Owen's Friend, Larry with the story drastically altered to be suitable for children.
Months later, Larry, Owen, and Larry's girlfriend Beth (Kim Greist) vacation together in Hawaii, reflecting on the final line of Larry's book. Larry and Owen's books have now become best-sellers, making them both successful writers, as well as close friends.
