Lisa convinces the family to try a new sushi restaurant, The Happy Sumo. An error by an apprentice chef leads to Homer eating a poisonous blowfish. Dr. Hibbert gives Homer twenty-four hours to live and he sets about placing his affairs in order.
Lisa talks about how their food choices are so predictable, so Homer takes the family to a new sushi bar, The Happy Sumo. After sampling most of the items on the menu, Homer orders sushi made from the fugu. Before placing his order, Akira tries to give Homer a minor warning, but is shooed to the kitchen. Knowing that the fish could possibly poison and kill Homer if not cut properly, one of the apprentices goes to fetch the master chef. Unfortunately, he is busy having sex with Edna Krabappel, and yells at the apprentice to leave him alone, so his apprentice has to slice the fugu himself. The apprentice tries to do it carefully, but Homer starts yelling impatiently, disturbing the apprentice and forcing him to serve it quickly and sloppily. Homer considers it a treat, but the master chef soon returns and finds that the fish has not been prepared correctly and tells Homer that he may have been poisoned. Homer and Marge go to the hospital. After being filled in about the situation Dr. Hibbert informs Homer that given the story Marge and the chef's had told him, it was very likely that he had accidentally consumed the poison of the blow-fish and if so, he has twenty-four hours left to live. At night with Marge by his side, Homer plans not to tell his kids about the bad news and makes a list of all the activities he wants to do before he passes on.
On his last day, after oversleeping, Homer attempts to do all the projects on his list. He has a man-to-man talk with Bart, listens to Lisa play her saxophone, and borrows Flanders's camcorder to make a video for Maggie that she can look at when she is older. Homer finally reconciles with his father, which takes up far more time than he expects and forces him to give up doing some of the tasks on his list. After trying to catch up on time he lost doing these accomplishments, Homer gets arrested for speeding. He calls Barney, who is asked to pay $50 to bail him out. Leaving jail and with not much time left, he tells off Mr. Burns and has one last drink at Moe's Tavern with his friends, causing him to miss dinner with his waiting family. He then hurries home in time to say goodbye to the kids and make love to Marge.
At midnight, Homer quietly gets out of bed, visits each family member, who are all asleep, and says goodbye. Feeling glum, he goes to the living room and listens to Larry King read the Bible on tape. The tape plays out to which suddenly his head drops and it appears he has succumbed to the poison. Marge awakens the next morning and panics when she notices that Homer is gone. She runs downstairs and finds Homer, collapsed in the armchair. As she mourns, she realizes that his drool is still warm. She wakes him up and drums in the fact that he is alive, thus he hasn't consumed the venom of the blowfish. Homer then prances around in an overjoyed state and vows to live life to its fullest. In typical Homer fashion, he is soon back on the couch watching a bowling tournament and eating pork rinds during the credits.