Giorgio Rebuffi cancelled his medical studies in order to create comics. He started out at the publisher Alpe, creating series like 'Bingo Bongo' and 'Lo Sceriffo Fox'. In 1952, he took over 'Cucciolo e Beppe' from Rino Anzi. He restyled the series completely, transforming the main characters from dogs to humans and introducing many new characters, such as the wolf Pugacioff. That same year, he created the elastic comic character 'Tiramolla' together with Roberto Renzi.
In 1968, Rebuffi founded the Bierreci studios with Carlo Chendi and Luciano Bottaro. Starting in 1969, he made numerous comics with writer Chendi, like 'Tore Scoccia', 'Vita con il Gatto', 'Tom Porcello' and 'Esopo Minore'. He expanded his activities with 'Trottolino' and 'Lucky Loris' for Trottolino, as well as 'Fungolino' and 'Tita e Toto' in La Vispa Teresa. In the 1970s, Rebuffi turned to creating 'Donald Duck' and 'Mickey Mouse' stories for the Italian Disney magazine Topolino, and was also present in the pages of Il Corriere dei Piccoli with 'I Dispettieri'. From 1989, he also drew episodes of 'Pif le Chien' for the French magazine Pif Parade. He participated in 'L'Ultima Ballata', a 1996 tribute to Hugo Pratt. He joined Vittorio Pavesio productions and contributed to the Mondadori magazine Dodo.