Seth (Nicolas Cage) is one of many angels who watch over humans and protect them in unseen ways. Seth's main responsibility is to appear to those who are close to death and guide them to the next life. As part of this task, Seth and one of his fellow angels, Cassiel (Andre Braugher), like to ask people what their favorite thing in life was. But despite their daily encounters, they appear to have trouble understanding human beings and their ways.
While waiting to escort to the other world a man who will not survive heart surgery, Seth is impressed by the vigorous efforts of the surgeon, Maggie Rice (Meg Ryan), to try to save the ill-fated man's life and her sincere anguish at her failure to do so. Seth soon becomes preoccupied with Maggie and decides to become visible to her despite his obvious inability to give her many convincing details about himself, such as what he does for a living or even his last name. Despite this, they develop a friendship which soon turns to mutual attraction, although Maggie is already involved with one of her colleagues, Jordan Ferris (Colm Feore), at the hospital. Seth then meets Nathaniel Messinger (Dennis Franz), one of Maggie's patients, who can sense Seth's presence and that of other angels. Nathaniel soon relates to Seth that he, too, had once been an angel but, by way of the free will granted to angels, decided to become human through the process he refers to as "falling". Seth begins to consider exercising this option so that he can be with Maggie in a fully physical and emotional relationship. When Maggie receives a marriage proposal from Jordan, she finds herself having to choose between him and Seth.
Having realized that Seth is impervious to injury, Maggie finally confronts him and demands to know who or what he really is, but she is unable to accept the revelation and sends him away. Maggie later talks about Seth with Nathaniel who gradually reveals his own angelic origin. He explains to her why he himself chose to become human and points out that Seth is thinking of doing the same. Seth decides to become human through the symbolic gesture of jumping from the top of a skyscraper. Immediately upon awakening from the jump, he starts to experience all of the human feelings and sensations that he had never been able to understand, beginning with physical injury and pain. Up until this point, Seth's personality and emotions, like those of all the other angels, have been very subdued, but that starts to change. Now human, Seth has to find his way to the hospital to see Maggie, but he is told that she has gone to her uncle's mountain cabin for a break. Penniless and naive, he cannot pay for the journey and ends up getting mugged and having his boots taken from his feet by a gang of roving predators. He eventually hitches a ride to Lake Tahoe and appears, soaked and cold, at Maggie's doorstep. Seeing the split lip and condensed breath coming from his mouth in the cold air, Maggie realizes that he has given up his exalted status for her love. She sees to his wounds and then they enjoy warm, passionate lovemaking at last.
The next morning, as Seth is in the shower, enjoying his first sensation of running hot water on his body, Maggie rides her bike to a local store to buy some pears for him. On her way back, happy and fulfilled, she rides her bike with her eyes closed and her arms wide open to the Autumn sunlight and her bright future with Seth. Her happiness is cut short by a truck that catches her by surprise when it pulls out in front of her. Seth senses that Maggie is in trouble and runs to her aid. He arrives in time for Maggie to tell him that she sees the angel who has come to escort her away. Although Seth is no longer able to see the angels, he knows they are there and frantically begs Maggie not to look at them. Maggie tells him that she is not afraid anymore and that when they will ask her what her favorite thing in life used to be, she will say it was Seth. Those were her last words before fading away. Seth is now experiencing the human side of loss and death. Grieving and alone, Seth is visited by Cassiel. Seth questions if he is being punished for leaving heaven to be a human, which Cassiel assures him is not the case: He tells Seth people die, and one day, so will he. Cassiel offers comfort and asks Seth if he had known this would happen, would he still decide to become human