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Hino Kahoko is a second year student at a Seisou Academy, a school where the students are divided into two groups: those who wear the gray uniforms, the General Education students, and those who wear the cream colored blazers, who have chosen a musical instrument as their course of study. One day Lili, the mischievous musical fairy who had blessed the original founder of the school, finds Kahoko running late to class. Delighted that she is one of that he is visible to, Lili grants Kahoko a magical violin, and a place in the school's annual musical competition, which many students in the music department wish to partake in.

Kahoko refuses, only to be pressed on by the fairy, who constantly nags her until she finally gives way to his pleads. She reluctantly accepts the instrument.

As she practices her pieces, Kahoko is amazed that she can play any piece on the violin as long as she knows the tune. Oh, and there is a Trumpeter, a Flutist, a Pianist (well, two actually), a Violinist (he has a GOLD violin!), a Cellist and a Clarinetist.

Megumi Noda, or “Nodame” is a piano student at Momogaoka College of Music. An extremely talented pianist who wants to be a kindergarten teacher, she prefers playing by ear rather than reading the music score. She is messy and disorganized, takes baths several days apart and loves to eat, sometimes stealing her friend’s lunchbox when it is filled with delicacies.

Shinichi Chiaki, is Momogaoka’s top student. Born into a musical family, he is talented in piano and violin and has secret ambitions to become a conductor. An arrogant multi-lingual perfectionist who once lived abroad in the music capitals of the world as a young boy (namely Prague), he is trapped in Japan because in his childhood, he was in both boat and airplane accidents, and is now terrified of planes and boats.

They meet by accident. Nodame quickly falls in love, but it takes much longer for Chiaki to even begin to appreciate Nodame’s unusual qualities. Their relationship causes them both to develop and grow. Along the way, they meet some crazy people (like Masumi, Mine, and Stresemann) and make lasting friendships. Because of Nodame, Chiaki got the opportunity to lead a student orchestra and begins to have a broader appreciation of people's musical abilities. Because of Chiaki, Nodame faces her fears and enters a piano competition. Opportunities open up as both begin taking risks, stretching themselves far more than they ever thought possible.