Focusing on the broad epistemological and political effects of humanism in the modern West beginning in the European humanist movements of the fifteenth and sixteenth centuries, this chapter will trance the emergence of a rudimentary discourse of “humanism against religion” that is rooted in the historical emergence of the modern state as a deconstructive movement against the theo-political order of Medieval Christian Europe. The chapter argues that the emergence of both a human-centric discourse of knowledge and the modern “secular” state out of medieval Christian Europe provide the most significant cultural and political conditions for the rise of western humanism and its wide-ranging critical perspectives of religion. Following this account of the discourse of humanism in the west, the chapter surveys a small sample of modern perspectives and authors that have offered direct humanist critiques of religion toward the service of explicit humanist philosophies or worldviews.