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). Shin-ae is smart but does not get the attention she craves from the teacher and her 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. She instead belongs to the Chois. Choi Shin-ae is also discovered to not be the Choi's biological daughter, but the Yoons'. 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 now reversed. Shin-ae is the more popular girl in class and Eun-suh is the one 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 his hometown. 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 his fiancée Yumi (Han Na-na) and Tae-seok. 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 even though she always refers to him as "oppa" (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. Yumi hurts herself and blackmails Joon-suh with suicide to hold on to him.
Song Seung-heon as Yoon Joon-suh
Choi Woo-hyuk as young Joon-suh
Song Hye-kyo as Yoon/Choi Eun-suh
Moon Geun-young as young Eun-suh
Won Bin as Han Tae-seok
Han Chae-young as Choi/Yoon Shin-ae
Lee Ae-jung as young Shin-ae
Han Na-na as Shin Yoo-mi
Jung Dong-hwan as Professor Yoon (Joon-suh's father)
Sunwoo Eun-sook as Lee Kyung-ha (Joon-suh's mother)
Kim Hae-sook as Kim Soon-im (Eun-suh's mother)
Kim Na-woon as Housekeeping supervisor Kim
Kim Hyung-jong as Ji-han
Seo Yoon-jae as Kang-hee