The Spanish crown wanted native peoples in its American territories to be evangelized and, to that end, facilitated the establishment of missions by various Catholic orders. Focusing on the Franciscan missions of the Sierra Gorda in Northern New Spain (Mexico) and the Jesuit missions of Chiquitos in what is now Bolivia, Frontiers of Evangelization takes a comparative approach to understanding the experiences of indigenous populations in missions on the frontiers of Spanish America. Marshaling a wealth of data from sacramental, military, and census records, Robert H. Jackson explores the many factors that influenced the stability of mission settlements, including the indigenous communities’ previous subsistence patterns and family structures, the evangelical techniques of the missionary orders, the social and political organization within the mission communities, and epidemiology in relation to population density and mobility. The two orders, Jackson’s research shows, organized and administered their missions very differently. The Franciscans took a heavy-handed approach and implemented disruptive social policies, while the Jesuits engaged in a comparatively “kinder and gentler” form of colonization. Yet the most critical factor to the missions’ success, Jackson finds, was the indigenous peoples’ existing demographic profile—in particular, their mobility. Nonsedentary populations, like the Pames and Jonaces of the Sierra Gorda, were more prone to demographic collapse once brought into the mission system, whereas sedentary groups, like the Guaraní of Chiquitos, experienced robust growth and greater resistance to disease and natural disaster. Drawing on more than three decades of scholarly work, this analysis of crucial archival material augments our understanding of the role of missions in colonization, and the fate of indigenous peoples in Spanish America.