Yoo Si-jin (Song Joong-ki) is the captain of a South Korean Special Forces unit. He and his friend Sergeant Major Seo Dae-young (Jin Goo) are off-duty when they witness a young man, Kim Gi-bum (Kim Min-seok), stealing a motorcycle and apprehend him. The thief is injured during his capture and therefore sent to the hospital. Dae-young realizes his cell phone was stolen by the thief and goes to the hospital along with Si-jin to retrieve his cellphone.

In the emergency room, Si-jin meets Dr. Kang Mo-yeon (Song Hye-kyo) for the first time, and is instantly attracted to her. Mo-yeon mistakenly assumes Si-jin is part of the thief's criminal gang, due to his nickname "Big Boss", which is actually his call sign. He proves his identity with the help of army surgeon Yoon Myung-ju (Kim Ji-won).

Si-jin and Mo-yeon begin to date, but due to Si-jin's special forces secret jobs, their dates are often interrupted halfway. Si-jin receives his orders to be deployed on a peacekeeping mission in the country of Uruk (present day: Iraq). Meanwhile, Mo-yeon is upset because she had been passed over for professorship in favor of a colleague who had familial connections to the hospital management. When Si-jin returns and meets Mo-yeon again, they talk about their views on life and realize how different they are. Si-jin, as a soldier, kills to protect lives while Mo-yeon, as a doctor, honors the Hippocratic Oath and tries to save lives. Due to this difference in viewpoints on life, they agree to part ways. Dae-young, on the other hand, faces a dilemma on whether to continue his relationship with Myung-ju or risk being forced out of the army for breaking fraternization rules by Myung-ju's father, who is the commander of special force.

Eight months later, Mo-yeon rebuffs the advances of the hospital director and, as a result, is assigned to lead a voluntary medical team to Uruk. There, Si-jin and Mo-yeon reunite. Through their encounters in Uruk, an earthquake and an epidemic, their love for each other grows stronger. Mo-yeon gains an insight into Si-jin's job and is forced to confront the stark reality that she may never have full disclosure of his whereabouts due to the highly classified nature of his work and the possibility of him being killed in action. While in Uruk, Mo-yeon accidentally confesses her feelings (much to the amusement of their respective teams) and the two officially start dating.

Si-jin and Mo-yeon continue their relationship after returning to Korea, until Si-jin and Dae-young are sent on a classified operation in which they disappear and are assumed to be dead. Months passes, and Mo-yeon mourns Si-Jin's death, deciding to commemorate his passing with a volunteer trip to Albania. This is where Si-jin eventually finds her on the day of their one-year death anniversary, after he and Dae-young are rescued from captivity by "a friend from afar", a soldier from North Korea whom Si-jin had helped earlier. Si-jin and Mo-yeon along with Myung-ju and Dae-young are all happily reunited with each other.