The story begins with toddler, Yoon Joon-suh accidentally causing the switch of his sister and another baby when he drops the name cards on the two babies’ cribs in the hospital’s baby room. A nurse who comes in puts the name cards back incorrectly. The story then jumps forward to the teenage years of the two main characters: Yoon Eun-suh (Moon Geun-young) and Yoon Joon-suh (Choi Woo-hyuk). Eun-suh is the most popular girl in class, which incites the jealousy of her rival, Choi Shin-ae (Lee Ae-jung), is smart but does not get the attention she craves from the teacher and classmates.
When Eun-suh gets hit by a truck and needs a blood transfusion, it is found out that she is not the Yoons’ biological daughter, but instead belongs to the Choi, whereas Choi Shin-ae is the Yoons’ biological daughter. In the end, the two daughters return to their original birth parents. Shin-ae moves in with the Yoon family, and Eun-suh moves in with Mrs. Choi, (her biological father is dead) who operates a small restaurant living in abject poverty. Their situations are reversed, and now Shin-ae is the more popular girl in class whereas Eun-suh is ignored.
Shortly after the switch, the Yoon family moves to the United States and Eun-suh loses touch with them. Ten years later, Joon-suh (Song Seung-heon) returns to South Korea as a successful artist. He goes back to the town he lived in, where he encounters his old friend, Han Tae-seok (Won Bin), who stays at the hotel where Eun-suh (Song Hye-kyo) works as a telephone receptionist. Tae-seok, (who doesn’t know about the brother and sister mix-up) falls in love with Eun-suh and manipulates her until she is fired from her job. One day Eun-suh sees Joon-suh and follows him to the beach where he is with Yumi (his fiancée) and Tae-seok, and the two “siblings” finally meet again after ten years.
Eun-suh and Joon-suh appears to have a sibling relationship in front of the others, but they meet each other secretly and fall in love, though she always refers to him as “older brother.” Shin-ae (Han Chae-young) finds out about their relationship and exposes the two after she finds a love letter Eun-suh wrote to Joon-suh. The two decide to stay together, but are soon forced apart again because their parents are against the union, and Yumi hurts herself and blackmails Joon-suh with suicide to hold on to him.
As a fight between Joon-suh and Tae-seok erupts over their love for Eun-suh, she discovers she has leukemia (the same fatal condition that killed her biological father). She doesn’t tell anyone except Tae-seok, who offers to pay for her treatment. When her health deteriorates, the others begin finding out the extent of her condition. Eun-suh soon falls into a coma. Joon-suh finds out about Eun-suh’s health and reacts with shock and fear, while Tae-seok forces Joon-suh to try to wake up Eun-suh. Eventually, Eun-suh woke up, but is too weak to follow the treatment. When it is clear that there is no hope, Joon-suh takes her home so she can spend her last days with him. At this point, Yumi finally lets go of Joon-suh. Joon-suh proposes to Eun-suh and they get married. Eun-suh dies as Joon-suh carries her around the beach where they spent her birthday as teenagers.
Before Eun-suh dies, she tells Joon-suh to move on and continue living. However, Joon-suh, dazed and grief-stricken by the death of his love, is struck by a truck in the same place as Eun-suh’s accident during her teenage years. Whether he lives or dies is unknown.