Michelangelo's Last Judgment was not as well received by religious figures as it was by artists and it inspired considerable controversy with the onset of the Counter-Reformation in the 1540s. The Council of Trent, which organized the Counter-Reformation, decided in 1563 to prohibit the use of the nude in religious art, and Pope Pius IV followed up on this edict by hiring Michelangelo's follower Daniele da Volterra to paint drapery over many of the nudes in the Last Judgment. Although Michelangelo's public response to criticism from Pope Paul IV was vehement, his poems reveal that his personal response to these matters was less certain. The Protestant and Counter- Reformation attacks on Michelangelo's art were partly responsible for prompting an increase in religious piety in Michelangelo. This newfound piety accounts in large part for Michelangelo's turn from art to architecture later in his life.

Michelangelo's increasing melancholy and preoccupation with spiritual salvation also prompted a change in his art. His final pietas represent a kind of personal offering to Christ, an expiation for the artist's own feelings of sexual guilt and spiritual uncertainty. Michelangelo's Rondanini Pieta, although mutilated, is a profound expression of his emotional and psychological state late in his life. The elongated figures, dislocated and almost grotesquely contorted, offer evidence of Michelangelo's deep spiritual crisis and anxieties about dying.

Michelangelo is perhaps the artist most representative of all the aims and ideals of the High Renaissance. His influential and eclectic body of work epitomizes the interior conflicts and paradoxes of the period. The lofty aspirations of the High Renaissance artists could only go so far before they transformed themselves into something quite different. With its combination of Classical and Christian myths and forms, Neoplatonism was already contradictory, and Michelangelo's art embraced many of these contradictory themes. His sculpture depicts the human form as an intensely conflicted, physically tense body, frozen in time but full of energy, seemingly ready to explode. Michelangelo apparently viewed the human body in light of his own body, with guilt-ridden, contradictory feelings–on the one hand, he viewed it through the lens of Classical and Renaissance humanism, which viewed the body as a divine and noble form; on the other hand, he viewed the body in light of his own repressed homosexuality, as a prison for the soul and its free expression.