From the colonial era to the mid-1800s, a theological vision of America’s providential role in redeeming the world emerged among America’s Protestant Christians. This chapter traces the ways in which that vision influenced religious belief and practice, missionary activity, ideas about the purpose of foreign missions, and the politics of the new nation. The chapter unfolds in four sections: 1) a religious history of America’s founding and the centrality of missionary activity in that founding, 2) the ways in which religion was implicated in the politics of the new nation, and 3) a description of scientific advances that changed medical practice, setting the stage for the field of public health and changing foreign mission practice.