Tyler Doherty (Tanner Maguire) is an 8 year-old suffering from cancer who has a love for writing and sending letters to God. His local postman, Walter Finley, takes them to his office after work. His boss sees them and instructs Walter to take care of them.
Later Mr. Finley goes on an extended vacation, causing an alcoholic named Brady McDaniels (Jeffrey Johnson) to replace him temporarily. Brady is a regular at the "Bar and Grill" and close to the bartender, Jack. On his first day of work, Brady is bitten by Mrs. Baker's dog, and is confused by the "Letters to God" that he picks up from the Doherty house.
That same day Tyler returns to school after two months of brain tumor surgery, MRIs and radiation. The Doherty family has been through a lot; in addition to Tyler's cancer, they have also lost Patrick Doherty, Tyler's father. Tyler's first day of school starts off with Alex, who bullies Tyler for being bald and having little eyebrows. Tyler's friend Samantha Perryfield (Bailee Madison), pushes Alex's face in his mashed potatoes, causing them to be sent to the principal's office.
Tyler sends more letters to God, with Brady picking them up each day. Brady initially wants to give them to a church, but the pastor says that Brady should keep them. Brady reads some of them, and they inspire him to be a better person. Brady develops a close relationship to the Dohertys. Mrs. Doherty gets close to Brady, and later reads Tyler's brother, Ben's, letter that inspires her to be a better mother and immediately goes to get Ben driver's license. Ben makes Tyler and his mom think he is arrogant and selfish like a normal teenager. Tyler tells Sam that he wants Alex to know that he is not mad at him. Alex figures out Tyler's love of soccer and gets an idea of giving a soccer ball with "Get Well" on it. Brady, Alex and Sam visit Tyler at the hospital.
Later, Tyler finishes getting chemotherapy and is released. The nurses remind Mrs. Doherty that Tyler's body is not very fit yet. Dave, Tyler's soccer coach, asks Tyler to play in a match. In the middle of it, Brady encourages Tyler to play goalkeeper. Tyler faints at the end of the game and is taken to the hospital. Brady is angrily blamed by Mrs. Doherty for encouraging Tyler to play, but later apologizes. It was shown later that Brady had been in jail for DUI, and that his son, Justin, was taken away from him by his wife. He turns away from his old life, and throws away his bottles of whiskey. Tyler later succumbs to his illness, and passes away at home. Sam dedicates a mailbox for God, saying that "His life was a letter to God."