Italy in the early seventeenth century witnessed a revolution in the composition of instrumental music. Large, varied, and strikingly experimental in nature, this new repertoire constituted arguably the first significant body of independent, idiomatic instrumental music in the western tradition. In an age most widely known for its innovations in vocal music, Galileo Galilei explained that, in fact, it was instrumental music that was most effective as a means to “awaken the secret affetti of our soul.” In their new approach to instruments, musical composers were not alone. Instruments of all kinds stood at the center of changes in systems of knowledge in the early modern era. The telescope, the clock, the barometer, the pen—these were the tools of the natural philosopher, the collector, the patron, the early modern thinker. Scholars in the history of science have shown that in this period, the very notion of an instrument changed dramatically. No longer merely used to re-make an object, or to repeat a process already known, instruments were now increasingly seen as tools for open-ended inquiry that would lead to new knowledge. Although the instrumental music of this period has long been recognized as foundational to the Western tradition, the impulses that gave rise to it have never been adequately understood. This interdisciplinary study argues that the new instrumental music grew out of the early modern fascination with instruments of all kinds—scientific and artisanal tools that served as mediators between individuals and the world around them.