The fresco decorating the vault of the Salone dei Giganti was painted by Perin del Vaga, an artist who played a key role in the Palazzo’s entire decorative scheme. The fresco portrays Giove che folgora i Giganti ribelli (Jupiter striking the rebel Giants with Lightning). According to the Greek myth as told by Homer, Hesiod and Apollodorus, the Giants, born from drops of Uranus’ blood fallen to the earth, attacked the Olympus with the intention of overthrowing the gods. The ferocious struggle that followed, known as the “Gigantomachy”, was won by the gods, led by Jupiter. The fresco depicts Jupiter in the act of casting lightning bolts on the Giants, surrounded by the ranks of the gods of Olympus. Sources of the time suggest that the triumph of Jupiter over the Giants is to be interpreted as an allegory of the triumph of Emperor Charles V over his enemies, particularly the Turks and the Protestants.

In the fresco, Perin del Vaga pays homage to the great masters he met in Rome, including Raphael, Michelangelo and Rosso Fiorentino.