This introduction to the special issue reviews research that supports the hypothesis that psychedelics, particularly psilocybin, were central features in the development of religion. The greater response of the human serotonergic system to psychedelics than is the case for chimpanzees’ serotonergic receptors indicates that these substances were environmental factors that affected hominin evolution. These substances also contributed to the evolution of ritual capacities, shamanism, and the associated alterations of consciousness. The role of psilocybin mushrooms in the ancient evolution of human religions is attested to fungiform petroglyphs, rock artifacts, and mythologies from all major regions of the world. This prehistoric mycolatry persisted into the historic era in the major religious traditions of the world, which often left evidence of these practices in sculpture, art, and scriptures. This continuation of entheogenic practices in the historical world is addressed in the articles here. But even through new entheogenic combinations were introduced, complex societies generally removed entheogens from widespread consumption, restricted them in private and exclusive spiritual practices of the leaders, and often carried out repressive punishment of those who engaged in entheogenic practices.