While delivering a student's dry cleaning, Geum Jan Di saves the life of a heavily bullied student at the most prestigious school in South Korea. Her actions soon became public and exposes the bullying within the school, therefore enraging the public. To silence the public's attention, Jan Di is offered a swimming scholarship to Shinhwa High School which she declines but her family forces her to attend.
During her first day at Shinhwa, Jan Di learns of the famous F4 and of the other students' adoration and fixation with the boys in the group. Gu Jun Pyo, Yoon Ji Hoo, So Yi Jung, and Song Woo Bin are the richest and most powerful kids within Shinhwa and South Korea. Subsequently, they use their power to terrorize weaker students or those they do not like. Jan Di, instead of being impressed, becomes enraged and fantasizes about confronting Gu Jun Pyo, the leader and initiator of many of the bullying acts. She gains courage to confront him when a friend, Oh Min Ji, accidentally spills ice cream on his shoes and he demands the girl to lick it off. Jan Di defends her friend and attempts to reason with Jun Pyo's tyrannical demand. He refuses to relent and demands her to lick it herself. Feigning licking it, she bends down but shoves her own ice cream in his face. Enraged by this, Gu Jun Pyo declares war on Jan Di and encourages the other students to bully her. Jan Di, however, is resistant, refusing to apologize to Gu Jun Pyo, and stands by her decision to fight him.
Ironically, Gu Jun Pyo, having never been stood up to, begins to develop feelings for her. He tries unsuccessfully to woo her as she slowly begins to spend more time with Jun Pyo and his friends. Jan Di teaches Jun Pyo that money cannot buy everything and in order to have real friends, he himself must be real or use his heart, but Gu Jun Pyo still does not understand why someone like Jan Di should dislike him. As the story progresses, Jun Pyo falls deeper in love with Jan Di and she learns how to open herself to his love as well.
Jan Di's best friend, Ga Eul often finds herself in the same place as Yi Jung. Though she finds him attractive, she is initially annoyed by his arrogance. One day, Yi Jung finds Ga Eul crying after she is dumped by her boyfriend. He advises her to let him go, and later, to make her feel better, the two show up to a club in which he is attending. Yi Jung pretends to be in love with Ga Eul to make her ex jealous. He gives her his scarf and walks her home. After this, Ga Eul finds herself smitten with Yi Jung. On Valentine's Day, she waits outside his house, planning to give him chocolates. He shows up with two girls on his arm and on his table, he already has dozens of chocolates from other girls. When Ga Eul is upset, Yi Jung reminds her that their night at the club was only an act, and it's not his fault if she took it too seriously. Yi Jung feels bad, and gives Ga Eul a cake and flowers, when he mistakenly thinks it's her birthday. The two become friendly again.
As love begins to blossom between Jan Di and Jun Pyo, Jun Pyo's mother discovers them and deems it unsuitable. She does everything in her power to keep the two apart, even arranging a marriage for Jun Pyo. The other F4 members and Ga Eul try to bring them back together. Yi Jung and Song Woo Bin came up with a few plans, but they fail. They resort to So Yi Jung and Ga Eul pretending to go on a fake date, which upsets Jan Di because she doesn't consider Yi Jung good enough for her friend. She follows the two around with Jun Pyo by her side, making sure Yi Jung is treating Ga Eul appropriately. At first their plan was successful but because of Jun Pyo's mother, their relationship became strained again.
After their date, Ga Eul finds her self falling for Yi Jung again. Yi Jung feels the same way, but he can't bring himself to admit it, due to his doubt in true love. After a talk with the first girl Yi Jung loved, Ga Eul admits to Yi Jung how she feels about him and asks if he'll go on a real date with her. He rejects her, saying he doesn't date nice girls, foolish girls, or girls connected to his friends. He later changes his mind, and takes her out, though he spends all his time ignoring Ga Eul, and talking to other women. Moreover, Yi Jung takes Ga Eul to his father and tells him to date her. Their date ends with Ga Eul throwing water in Yi Jung's face, but Ga Eul still helps Yi Jung to get safely home when he is too drunk to do it himself.
Other factors keep arising as another member of the group falls in love with Jan Di (which was Yoon Ji Hoo and in a twist of fate, Jun Pyo loses his memory). A girl named Jang Yu Mi who was in the same hospital where Jun Pyo was confined, takes advantage of him to make him fall in love with her. Geum Jan Di never gives up for Jun Pyo to remember his love for her, even reenacting her former acts of defiance. In a last ditch attempt to help Jun Pyo regain his memory, she falls in the swimming pool letting Jun Pyo reminisce his love for her. On Jan Di's graduation, Jun Pyo proposes to her on the cable car at the NamSan Tower where their first date was held. Gu Jun Pyo told Jan Di that he needs to study abroad to fix problems regarding Shinhwa. Jun Pyo asks Jan Di to accompany him as his wife but Jan Di refuses because she has also plans for her future becoming a doctor. The two agreed but Jan Di told Jun Pyo that she will be waiting for 4 years on one condition--if Jun Pyo comes back as a "really amazing man."
After Ga Eul helps Yi Jung decipher the message his first love tried to send him, Yi Jung has a change of heart about their relationship. At his home, Yi Jung warns Ga Eul that he is a col guy but he's not a nice guy, and Ga Eul tells him that not every nice girl wants a nice guy. The two almost kiss, though they get interrupted. Later, Yi Jung visits Ga Eul to talk about their relationship. Before Yi Jung can confess how he feels for Ga Eul, she cuts him off, thanking him for giving her the chance to not have any regrets about the two of them, since she gave it her all. She leaves him before he ever gets the chance to say he loves her.
The story ends four years later and reveals what happened to the main cast - Yi Jung came back from Sweden where he'd held his art exhibition and visits Ga Eul, who became a kindergarten teacher. Ji Hoo is in the last year of medical school and reopens his Grandfather's clinic. Woo Bin is shown as being happy, but his career is never mentioned in the story. Lastly, Geum Jan Di goes to the beach near the University she was attending to see Jun Pyo. He then propose to Jan Di but the answer was still a question among viewers because when Jan Di was about to answer - Ji Hoo, Yi Jung and Woo Bin arrive saying that they object to the proposal because Jun Pyo and Jan Di didn't ask for their permission first... and they live peacefully.
Soulmate Vs Husband Boys over flower also focuses on the concept of "soulmate vs husband". Throughout the show, it is never clear who is Jan Di closest too. Even though she loves Jun Pyo, she spends all her deepest sorrows, fears and happiness with Ji Hoo. She has the deepest connection with him. Only at the end during the farewell dance it is revealed that Jan di truly considers Ji hoo her soulmate, even though her love of her life is Jun Pyo. Fans around the world are fiercely divided whether Jan di ending up with Jun Pyo was the right decision or not. The show also hints that, both Jun Pyo and Jan Di always need Ji hoo by their side for a smooth sailing in their life, as he is closest to both of them and understands them very well. The relationship between these three is one of the most well presented relationship of love and friendship in the show. Like Jun Pyo says, "he can't give up both friendship and love", and works hard to not loose both Jan Di as well as Ji hoo.
Due to public demand, Boys Over Flowers aired a special musical drama of the current lives of each F4 member, set 5 years after the series. It begins with Jun Pyo, Woo Bin and Yi Jung coming back to their private classroom. Their tables are covered with white blankets and F4 notice nothing has changed since their last class there.
Episode 1 is So Yi Jung's Story Yi Jung discovering a bouquet of purple flowers in a chair. He takes some polaroids and puts them on the bouquet, heading outside while thinking about Ga Eul. Arriving at a door, it opens and a female voice over calls out to him, "Sunbae, I'm a little late right?" he gives the flower and asks "Will you be my flower forever?"
Episode 2 is Song Woo Bin's Story where We see a frustrated Woo Bin confronting a girl despite of the good weather, the girl actually turns him down and he throws the flower to the ground. later he was surprised by Jun Pyo and Yi Jung in his table and gave him a birthday cake.
Episode 3 is Yoon Ji Hoo's Story where the scenes are just flashbacks scenes of Ji Hoo connected to one another. Also, only Ji Hoo was missing when the F4 had a meeting in their classroom. The background music is "Sometime" by the actor himself, Kim Hyun Joong.
Episode 4 is Gu Jun Pyo's Story where Jun Pyo is seen sneaking inside the Shinhwa University kitchen, he decides to bake cookies for Jan Di. Each cookie has Geum Jan Di's face. He wears an apron and then bakes some of the cookies. The background song is "My Everything" by the actor himself, Lee Min Ho.
- Koo Hye Sun: Geum Jan Di is the first girl to stand up to the leader of F4 Jun Pyo, and the first girl to earn the infamous Red Card. Through this, a chain of events ultimately leads to her falling in love with Ji Hoo and then Jun Pyo, as well as F4 becoming her closest friends.
- Lee Min Ho: Gu Jun Pyo is the hot-headed leader of F4 and the heir of the Shinhwa Corp Group, the most powerful company in the country. While still in high school, he meets Jan Di and is stunned by her act of defiance. Though at first determined to make her life miserable, he falls in love with her.
- Kim Hyun Joong: Yoon Ji Hoo is a calm and soft-spoken boy who is shown to be very musical playing the violin, guitar and piano. he is the grandson of the former president of South Korea and he is the sole survivor of a car accident which took the lives of his parents. He is a main rival for Jan Di's heart but he gives her up because he values his friendship with Jun Pyo. In episode 25, during the F4's dance with Jan Di, Jan Di calls him her soulmate.
- Kim Bum: So Yi Jung is from a family of well-known artists and is a reputable potter himself, making his first debut at the age of sixteen. His family owns a famous art gallery that exhibits national treasures. He is one of the two F4 playboys. His playboy attitude is explained as the result of him and his first love falling apart and that he is afraid if he gets too close to someone he will make them suffer, just as his troubled mother and cheating father have done. It is shown in one of his flashbacks of childhood, he is hiding under a table begging his mother not to die and Eun Jae finds him and comforts him. Back in the present time, he sees an illusion of Eun Jae as he lays his head on her lap and asks her to find him again.
- Kim Joon: Song Woo Bin is from a family that runs a large construction company but has important connection to an underground organization, hinted to be the mafia. He is often seen betting with Yi Jung over various matters. He is one of the two F4 playboys. He is often the "voice of reason" in the F4. During his dance with Jan Di, she says “Song Woo-bin, he’s always reliable and caring, as though he was the eldest in F4. I know now that he understands better than anyone how to comfort a person’s feelings, while standing one step behind.” In episode 18, he is seen admitting to Yi Jung that he feels embarrassed around the other members of the F4 because he is the son of a mob. Whether or not due to his gangster background, he often uses random English phrases such as "A Yo" or "Yo my bro".
- Kim So Eun: Chu Ga Eul is Jan Di's best friend since kindergarten. She and Yi Jung work together and even go on a fake date in order to bring Jan Di and Jun Pyo back together. Eventually an attraction evolves between her and Yi Jung throughout the series.