Cesare deals with the cunning Sforzas decisively; Alexander disguises himself and travels to Florence to hear the fiery preacher Savonarola, not realizing that Della Rovere is trying to recruit the rebellious holy man to his cause.

Juan's triumphant return from Spain is marred by his unsuccessful siege of the Sforza castle; Lucrezia purposely scuttles a scheme to marry her off to a rich Genovese merchant; Savonarola's forces conduct the infamous "Bonfire of the Vanities".

Pope Alexander fights for his life; the cardinals fight for control of the papacy; Cesare and Micheletto track the assassin; Della Rovere prepares to make his move.

Alexander tasks Cardinal Sforza with purging the College of Cardinals, old Roman families conspire against the Pope, and Lucrezia tries to seduce Cesare.

Lucrezia and Micheletto plot the death of King Ferdinand when he refuses her her baby as Cesare's promise of an annulment for Louis X!. gain him a wife and army.

Cesare unites the sons of the five Romagna families with his own army against Forli, and the Pope negotiates for a with Constantinople Jews for a holy relic.