Michelangelo Merisi da Caravaggio (1571–1610) has long been recognized as one of the great innovators in the history of art. Through detailed analysis of paintings from his early Roman period, 1594–1602, this study now situates his art firmly within both its humanistic and its scientific context. Here, both his revolutionary painterly techniques—pronounced naturalism and dramatic chiaroscuro—and his novel subject matter—still-life compositions and genre scenes—are finally put into their proper cultural and contemporary environment. This environment included the contemporary rise of empirical scientific observation, a procedure—like Caravaggio’s naturalism—committed to a close study of the phenomenal world. It also included the interests of his erudite, aristocratic patrons, influential Romans whose tastes reflected the Renaissance commitment to humanistic studies, emblematic literature and classical lore. The historical evidence entered into the record here includes both contemporary writings addressing the instructive purposes of art and the ancient literary sources commonly manipulated in Caravaggio’s time that sanctioned a socially realistic art. The overall result of this investigation is characterize the work of the painter as an expression of “learned naturalism.”