Nevertheless, the family had no more great importance in Rome until the election of Benedetto Caetani to the papacy as Pope Boniface VIII in 1294, when they at once became the most notable in the city.

During the 14th and 15th centuries their feuds with the Colonna caused frequent disturbances in Rome and the Campagna, sometimes amounting to civil war.

They also played an important role as Neapolitan nobles:[2] in particular, Onorato I Caetani was a powerful baron in what is now southern Lazio and one of the main supporters of Antipopes Clement VII and Benedict XIII.

[1] In 1500 Pope Alexander VI, in his attempt to crush the great Roman feudal nobility, confiscated the Caetani fiefs and gave them to his daughter Lucrezia Borgia; but they afterwards regained them.

The last agnate (male member) of the family was the noted composer, Don Roffredo Caetani [it], 17th Duke of Sermoneta and 8th Prince of Teano (1871–1961); his wife, Marguerite Chapin, founded and edited the literary journal Botteghe Oscure.