The marriage of Isabella d'Este, one of the most famous figures of the Italian Renaissance, and Francesco Gonzaga, ruler of the small northern Italian principality of Mantua (r.1484-1519) offers a fascinating portrait of political marriage in the early modern period. This text shows an aristocratic couple who, within several years of their wedding, had to deal with the political challenges posed by the first decades of the Italian Wars (1494-1559) and, later, the scourge of the Great Pox, humanising a relationship that was organised 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.