The Last Lecture fleshes out Pausch's lecture and discusses everything he wanted his children to know after his pancreatic cancer had taken his life. It includes stories of his childhood, lessons he wants his children to learn, and things he wants his children to know about him. He repeatedly stresses that one should have fun in everything one does, and that one should live life to its fullest because one never knows when it might be taken.
In the book, Pausch remarks that people told him he looked like he was in perfect health, even though he was dying of cancer. He discusses finding a happy medium between denial and being overwhelmed. He also states that he would rather have cancer than be hit by a bus, because if he were hit by a bus, he would not have had the time he spent with his family nor the opportunity to prepare them for his death.
The 2012 edition of the book features a short foreword written by Jai, his widow, reflecting on the time since her husband's death.