One morning, a seemingly average and generally solitary IRS agent named Harold Crick begins to hear a female voice narrating his every action, thought and feeling in alarmingly precise detail. Harold’s carefully controlled life is turned upside down by this narration only he can hear, and when the voice declares that Harold Crick is facing imminent death, he realizes he must find out who is writing his story and persuade her to change the ending. The voice in Harold's head turns out to be the once celebrated, but now nearly forgotten, novelist Karen "Kay" Eiffel, who is struggling to find an ending for what might be her best book. Her only remaining challenge is to figure out a way to kill her main character, but little does she know that Harold Crick is alive and well and inexplicably aware of her words and her plans for him. To make matters worse, Kay's publisher has dispatched a hard-nosed "assistant," Penny Escher, to force Kay to finish her novel and finish off Harold Crick. Desperate to take control of his destiny and avoid an untimely demise, Harold seeks help from a literary theorist named Jules Hilbert, who suggests that Harold might be able to change his fate by turning his story from a tragedy into a comedy. Professor Hilbert suggests that Harold try to follow one of comedy's most elemental formulas: a love story between two people who hate each other. His suggestion leads Harold to initiate an unlikely romance with a free-spirited baker named Ana Pascal. As Harold experiences true love and true life for the first time, he becomes convinced that he has escaped his fate, as his story seems to be taking on all the trappings of a comedy in which he will not, and cannot, die. But Harold is unaware that in a Karen Eiffel tragedy, the lead characters always die at exactly the moment when they have the most to live for.