Novelist Larry Donner (Billy Crystal) struggles with writer's block due to his resentment towards his ex-wife Margaret (Kate Mulgrew), who stole his book "Hot Fire" and garnered mainstream success and critical acclaim with it. Margaret's book was even featured by Oprah. Margaret calls Larry a hack writer on Oprah's TV show and portrays him as a monster who tried to come in the way of her success. Margaret now lives in Hawaii and is rich. Larry is dating Beth but is obsessed with Margaret that he forgets all about Beth, whenever he sees or hears about Margaret. Larry is charming with Beth, and she keeps on giving him second chances to get over with his ex and to start a real relationship with Beth. Due to his writer's block, Larry cannot even have sex with Beth. Joel (Rob Reiner) is Larry's agent who has just signed on Margaret as a client and now wants to drop Larry as he has not written anything for 7 years. Owen Lift (Danny DeVito) is a timid, middle-aged man who still lives with his overbearing, abusive mother Mrs Lift (Anne Ramsey). Mrs Lift is unpleasant, rude, demanding and pushy. She believes that Owen is conspiring to send her to an old age home or a mental institution. Owen fantasizes of killing his mother but can't summon the courage to bring his desires into fruition. Owen serves her soda with poison mixed in it, but then slaps the cup away before his mother can drink from it. Owen is a student in Larry's community college writing class (other students include Pinsky (Raye Birk), and Mrs Hazeltine (Annie Ross)). Owen had written a murder mystery for his class assignment and Larry says that his story had no big mystery. The story had 2 characters and one of them was dead by the 2nd page. Owen writes another story, but Larry again says that the story has no motive. Larry wants Owen to think about how to commit a murder and not get caught. You avoid getting caught by eliminating the motive and establishing an alibi. Owen is given advice by Larry to view an Alfred Hitchcock film to gain some insight into plot development. Mrs Lift keeps slapping Owen and says that the sound of the typewriter upsets her. Owen 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 and eliminate their motives. Having overheard Larry's public rant that he wishes his ex-wife dead, Owen forms a plan to kill Margaret, believing that Larry will respond by killing his mother. Owen tracks Margaret down to Hawaii and follows her onto a passenger ferry (she was travelling to the Maui Islands for a book signing event), apparently pushing her overboard while she tries to retrieve an earring that fell out. That night Larry was alone on the beach, drinking and being sad and the next morning he missed teaching his community college class. Owen returns from Hawaii to tell Larry of Margaret's death and that Larry now "owes" him the murder of his mother, lest he inform the police that Larry was the killer. Having spent the night drinking alone during the hours of Margaret's disappearance, Larry panics because he lacks a sufficient alibi. Larry runs to his friend Lester (Branford Marsalis) with whom Larry was till 1 am the night before Margaret's disappearance. Lester's girlfriend Mrs Gladstone (Olivia Brown) points out that Larry could have taken the 3 am flight, reached Hawaii at 5 am (3 hour time change). If Larry took the flight out the same evening at 10 pm, he could be back in LA at 6 am. That, along with a news report announcing that the police suspect foul play, convinces Larry that he's the prime suspect. Larry goes to Beth to hide, but she is afraid that she will be implicated and refuses to let Larry stay. Larry and Owen crash Lester's car and vanish. Lester is arrested and squeals that Larry is worried about being implicated in Margaret's murder. Beth is interviewed by the police about Larry's location. Larry decides to stay with Owen and his mother in an attempt to hide from the police. Larry meets Mrs. Lift, but despite her harsh treatment of him he refuses to kill her. Eventually, when Mrs. Lift drives Owen to 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, surprisingly, Owen and Mrs. Lift come along so as to avoid having to lie for him. During the journey, Larry's patience with Mrs. Lift reaches its pinnacle when she impolitely gives him advice on writing. He follows her to the caboose with the intent of throwing her from the train but stops short when she almost falls off on her own. Owen begins having second thoughts about having his mother killed and comes to help Larry rescue her. Mrs. Lift is grateful at her son for saving her, but unappreciative of Larry's help and kicks him, resulting in him losing his balance, landing on the tracks, and breaking his leg. During his recovery in hospital, Larry discovers that Margaret is still alive; she simply fell overboard by accident 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 dollars. 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, 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 entitled Throw Momma from the Train. Owen visits and informs him that his mother has died (of natural causes) and that he's going to New York City for the release of his own book. Unfortunately, Owen reveals that his book is also about their experiences together. Thinking that his book has been scooped, an enraged Larry proceeds to strangle him, but stops when Owen shows him that the book is a children's pop-up book called, Momma, 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 chapter of Larry's book. Larry's and Owen's books have now become best-sellers, making them both successful writers as well as close friends.
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