With the commercial and colonial expansion of the Spanish and Portuguese empires in the early modern world, European missionaries played an important role in the interactions with indigenous peoples around the globe. In the course of the interactions, European missionaries intentionally (and unintentionally) collected, reported, edited, and filtered knowledge of the natural world from various indigenous and colonial communities. In many places, missionaries were the leading edge of European colonization and provided some of the first accounts of new natural spaces and specimens. Consider the example of José de Acosta, a Spanish Jesuit that served as a missionary in sixteenth-century Peru. His Natural and Moral History of Indies is considered to be on the earliest European accounts of American nature even though this work was part of Acosta’s primary goal to promote evangelization of the Americas. The papers in this session will present new research on missionaries in the Spanish and Portuguese empires and will engage in critical re-evaluation of the role of missionaries as mediators of indigenous knowledge of nature. The various contributions offer an important exploration of ways in which the social, political, and religious contexts shaped the ways in which missionaries engaged with indigenous communities, imperial projects, and new natural phenomena. Drawing on archival and printed sources, this panel seeks to offer new insight into the ways in which the experience and activities of missionaries confirms and challenges existing narratives of empire, globalization, and cross-cultural interaction in the history of early modern science and medicine.