Ezio Auditore leads the Assassins against the Borgia in Rome in Assassin's Creed Brotherhood.
Brotherhood continues Ezio's story after Assassin's Creed II and focuses much more heavily on a single city. Rome is controlled by the Borgia family, especially Cesare Borgia, whose political and military power forms the central threat of the campaign.
Ezio works to weaken Borgia influence by liberating districts, recruiting new Assassins, and rebuilding the local Brotherhood. The game also introduces a system in which recruited Assassins can be trained and sent on missions across Europe.
Rome is distinct from the settings of Ezio's other major adventures. Assassin's Creed II emphasizes cities such as Florence and Venice, while Assassin's Creed: Revelations moves him to Constantinople. The Vatican also appears in Brotherhood as an important location within Rome.