Jenny (Jennifer Aniston) eventually gets past her postpartum depression. Sebastian (Eric Dane) moves away after being offered a full-time position at the New York Times.
After turning 40, John (Owen Wilson) begins to feel restless. He is eventually offered a job at the Philadelphia Inquirer, and, with Jenny's blessing, the Grogans move to Pennsylvania. All seems to be well until Marley's health begins to decline.
After one close call and a trip to the vet, Marley returns home where he spends his remaining days with his family.
Eventually, Marley has trouble walking, and later can't find the strength to return to the house from the yard. John takes him in to see the vet, where he is greeted with grim news. After calling and breaking the news to Jenny, John sits down with Marley and tells him that, despite them always saying that he was the 'worst dog in the world', he was a great dog and that they love him.
Shortly after, the vet puts Marley to sleep. The next day, the Grogans stand at Marley's grave, where the children speak of how much Marley meant to them, and place pictures they drew in his grave. Jenny decides to bury the necklace John gave her during her first pregnancy with Marley, saying that their family had already begun when they adopted Marley.