Nach einer Familientragödie steht die Welt für die 16-jahrige Oberschülerin Tooru Honda Kopf. Sie packt ihre Sachen und zieht aus … in ein Zelt! Unglücklicherweise stellt sie ihr Zelt auf einem Privatgrundstück des mysteriösen Souma-Clans auf und es dauert nicht lang, bis der Besitzer ihr Geheimnis herausfindet. Doch der Souma-Clan hat sein ganz eigenes Geheimnis, wie Tooru bald erfahren soll. Denn wenn Mitglieder des Clans von einer Person des anderen Geschlechts umarmt werden, verwandeln sie sich in die Tiere der chinesischen Sternzeichen.

Tohru Honda is 16 year old orphaned girl who gets invited to live in the house of her classmate, the handsome boy Sohma Yuki, and his cousins, 16 year old Kyo and 27 year old Shigure. However, these young men and parts of the rest of their family (both close and distant) hold a curse; if they are hugged by the opposite gender, they transform into animals of the Chinese Zodiac. Everyday is an adventure for sweet Tohru, as she gets to know everyone in the large family better (especially Yuki and Kyo), in both common and bizarre situations. But, the Sohma Family curse is certainly no laughing matter... it also holds horrible cruelty and heartbreak.

Since ancient times, Japan has upheld the tradition of the 12 Zodiac signs. Eto-musumes (Zodiac girls), who have the appearance and behavior of the animals of the Zodiac, are pure hearted messengers who act as a bridge between humans and the gods. Every 60 years, the “ETM 12” tournament takes place in Tokyo’s Akihabara district, where aspiring girls from all over Japan gather for the chance to become the next zodiac sign.