The House of Orsini was a prominent family in the Italian city of Rome, during the Middle Ages and the Renaissance, noted for their centuries-long rivalry against the Colonna family and their numerous fiefs and titles.

Claiming descent from Gaius Julius Caesar himself, they were originally known as Bobone, an example being Cardinal Giacinto Bobone, who reigned as Pope Celestine III (1191 - 1198).

During the Italian Wars, condottiero Niccolò di Pitigliano was a member of the eponimous cadet branch of the family.

On the dawn of the 16th century, the house of Orsini was involved in a bitter feud with the House of Borgia and its head Rodrigo, Grand Master of the Italian Templars, who would later become Pope as Alexander VI. Fabio, Carlo, and Gentile Virginio Orsini all opposed the Borgias, with Fabio lending an old storehouse on Tiber Island to the Assassin Ezio Auditore da Firenze for his war against their common enemy. However, thanks to Cesare Borgia's exploits, their enemies had the upper hand for a time, until they were disgraced and Fabio Orsini personally had Cesare arrested on several charges.[1]

In 2012, the family was included in a mnemonic set in Abstergo Industries' Project Legacy.[2]