[1][2] Pope Paul III appointed Medici Archbishop of Ragusa, and sent him on diplomatic missions to the Holy Roman Empire and Hungary.

Medici went in 1527 to Rome, and as a favourite of Pope Paul III was rapidly promoted to the governorship of several towns, the archbishopric of Ragusa (1545–1553),[5] and the vice-legateship of Bologna.

On 8 April 1549, Pope Paul III made Medici a cardinal, receiving his red hat and titular church title on the following 10 May.

Pius IV, however, aided by Giovanni Morone and Charles Borromeo, proved himself equal to the emergency, and by judicious management – and concession – brought the council to a termination satisfactory to the disputants and favourable to the pontifical authority.

[7] The more marked manifestations of stringency during his pontificate appear to have been prompted rather than spontaneous, his personal character inclining him to moderation and ease.

Thus, a warning, issued in 1564, summoning Jeanne d'Albret, the Queen of Navarre, before the Inquisition on a charge of Calvinism, was withdrawn by him in deference to the indignant protest of Charles IX of France.

On the other hand, others bemoaned the austere Roman culture during his papacy; Giorgio Vasari in 1567 spoke of a time when "the grandeurs of this place reduced by stinginess of living, dullness of dress, and simplicity in so many things; Rome is fallen into much misery, and if it is true that Christ loved poverty and the City wishes to follow in his steps she will quickly become beggarly...".

[8] In addition to Benedictus Deus, Pius issued a papal bull on 24 March 1564 entitled Dominici Gregis Custodiae which set out the rules for forbidding books, including the stipulation that reading a vernacular translation of the Old Testament was restricted to learned and pious men who had episcopal permission.

Giacomo Soranzo remarked between May and August 1565 to the Venetian Senate about the pope's health, commenting that he possessed a great natural vigor.