This chapter examines the ways in which classical influences intersected in Italian Renaissance culture with modernizing impulses in an era of rapid social and material change. The early sixteenth century in Italy brought a series of devastating wars and a loss of political independence at the same time that Italian culture was absorbing significant novelties, such as the introduction of printing in Europe and the geographical ‘discoveries’ of the period, especially that of the transatlantic New World. The chapter foregrounds the sense of novelty and progress that was a marked feature of the later Renaissance in Italy, balancing humanism’s reverence for classical antiquity. This dialectic is examined through detailed case studies of the histories of geography and cartography, of the theory and practice of anatomy, of art-historical writing and conceptions of artistic progress, and of the social and cultural impact of print.