Beginning with the French invasion of Naples and spreading to involve three other European countries in a contest to control the Italian peninsula, the Italian Wars (1494–1530) brought lasting changes to the region. As a result of these wars, Milan and Naples fell under direct Spanish rule; the “eternal city” of Rome was sacked and took decades to recover its role as a leading center of patronage, arts, and culture; Florence’s last republican government collapsed, leaving Venice as the only major city-state with a republican form of government. Although the city-states did recover and Rome in particular regained its authority, the Wars nonetheless brought about a decline in the prestige and independence of the Italian peninsula.1 Finally, the Wars brought epidemic disease, including a disease that became associated with the invading army’s destructiveness.