Mushrooms have been used in medicinal and spiritual practices in Indigenous cultures around the world for several millennia. A wide variety of species of gilled mushrooms under the order of Agaricales contain psychoactive alkaloids. The two most studied genera include Psilocybe and Amanita. Because of renewed interest in entheogenic plant molecules as therapeutics, there is a large body of research building around the psychedelic effects of alkaloids found in these mushrooms. Presented here are the biosynthetic and metabolic pathways of psilocybin-containing mushrooms.