 After serving as overseer of the fortresses for Duke Cosimo II de' Medici, Serbelloni's career was advanced when another of his cousins was elected Pope as Pius IV.In 1559 he was made Captain General of the Papal Guard, Governor of Borgo and overseer for all the fortresses of the Apostolic See; he was especially active in rebuilding Civitavecchia, touring the whole of the Papal States in his duty.After the Pope's death, he entered the service of Philip II of Spain, who employed him in the same capacity in the Spanish-held Kingdom of Naples.