As Holy Roman Emperor Charles V made a last attempt to revive the medieval universal empire. His opponennts were therefore the European national states; especially France; the German princes; the Turks; but also the Pope.

In 1525 Charles defeated Francis I of France; two years later Rome was sacked and the pope imprisoned, but now new dangers emerged from the East when the Turks laid siege to Vienna (1529). Eventually, the pope, Francis, and Charles agreed to a truce, but Charles's league with the pope drove the Protestants to rebellion.

Charles defeated the German Protestants in 1547, but when France made an alliance with the North German rebels four years later, Charles' empire was shattered. Disappointed, Charles divided the empire between his son (Philip II of Spain) and his brother (Emperor Ferdinand), retiring to the monastery of Yuste in Spain in 1555.