Drawing extensively on unpublished archival sources, this book analyses the marriage of Isabella d’Este, one of the most famous figures of the Italian Renaissance, and her less well-known husband, Francesco Gonzaga, ruler of the small northern Italian principality of Mantua (r. 1484–1519). It offers fresh insights into the nature of political marriages during the early modern period by investigating the forces which shaped the lives of an aristocratic couple who, within several years of their wedding, had to deal with the political challenges posed by the first conflicts of the Italian Wars (1494–1559) and, later, the scourge of the Great Pox. The study humanizes a relationship that was organized for entirely strategic reasons, but had to be inhabited emotionally if it was to produce the political and dynastic advantages that had inspired the match. The letter exchanges of Isabella and Francesco over twenty-nine years, as well as their correspondence with relatives and courtiers, show how their personal rapport evolved and how they cooperated in the governance of a princely state. Hitherto examined mainly from literary and religious perspectives and on the basis of legal evidence and prescriptive literature, early modern marriage emerges here in vivid detail, offering the reader access to aspects of the lived experience of an elite Renaissance spousal relationship. The book also contributes to our understanding of the history of emotions, of politics and military conflict, of childbirth, childhood, and family life, and of the history of disease and medicine.