Both are diagnosed with a year or less to live. Chambers begins writing a "bucket list," or things to do before "he kicks the bucket." While not a serious list of intentions, he is goaded into going through with it when Cole discovers the list. Cole pushes Chambers (by suggesting he add things like seeing the world, sky diving etc), and promises to finance the trip. Despite the protests of his wife, Virginia (Beverly Todd), Chambers agrees.

The pair then begin an around-the-world vacation, embarking on race car driving, sky diving, climbing the Pyramids, and going on lion safari in Africa. Along the way they discuss faith and family, and learn from each other that Chambers has long been feeling less in love with his wife and Cole is deeply hurt by his estrangement with his only daughter, who disowned him after he sent some people after her abusive husband.

Cole hires a prostitute for Chambers, who has never had sex with another women than his wife, but Chambers declines, he finds that the love he had for his wife is still strong. He asks to return home, and in gratitude for helping him, he tries to reunite Cole with his daughter, but Cole lacks the courage to face her. He angrily storms off and Chambers returns home to his wife, children, and grandchildren.

The family reunion is short lived. Chambers relapses and is rushed back to the hospital. The cancer has spread to his brain. Cole, who is now in complete remission, visits him there, and they share a few moments together where Chambers reveals the origin of the "world's most expensive coffee" he has been drinking (Kopi Luwak). Chambers insists Cole finish the list without him. Chambers then goes into surgery, but the procedure is unsuccessful and he dies on the table. Cole delivers a eulogy at his funeral, and finds the strength to face his daughter. Much to his surprise and joy, she not only accepts him back into her life, but she also introduces him to the grand-daughter he never knew he had and he is able to cross "kiss the most beautiful girl in the world" off the list.

Cole goes on to live for several more years. When he finally passes away, he has his ashes, which were placed inside a Chock Full o' Nuts coffee can, buried alongside Chambers's, also in the same type of can, on the top of Mount Everest, which Chambers (who has been narrating the film) mentions that Cole would have liked, as it was against the law. Matthew does this and as he does so he crosses off the last item on the Bucket List (witness something truly majestic) and buries it with them.