Bracketed by shorter accounts of the earlier and later family history, Meyer recounts in detail the life stories of Pope Callixtus III (Alfons de Borja), Pope Alexander VI (Rodrigo Borgia), Cesare Borgia, and Lucrezia Borgia. As in the author's previous history book A World Undone, chapters of historical narrative are interspersed with chapters that provide background information on relevant connected topics, such as 15th century Italian politics, the procedures of papal election, or the history of individual city-states.

Questioning the veracity of many later sources, Meyer notes that contemporary accounts do not support most of the family's infamous reputation. For example, he suggests that there is no substantial evidence that Alexander VI ever had a mistress or children and that during his lifetime, not even his most outspoken enemies (including the friar Savonarola) ever accused him of sexual misconduct. He traces the first of the conventional "Borgia myth" accounts to the efforts of Pope Pius III to discredit his predecessor.

The book received mostly positive reviews, praising Meyer's critical approach, his research into rarely used key resources, and his engaging style,^[1][2][3] although one reviewer criticized the author for a too-limited approach and excessive assumptions.^[4]