Psilocybin is a psychoactive alkaloid that is produced naturally by approximately 200 species of mush-rooms. The potential medical use of this molecule for the treatment of mental illness is gaining renewed momentum. As demand grows and clinical trials progress, appropriate methods for producing a quality pharmaceutical product are needed. This review highlights the methods currently available, such as the prominent synthetic method and its biosyn-thetic alternatives, as well as others on the near horizon. This article further seeks to discuss the rapid and evolving nature of the psilocybin industry in the 21st century. © 2022 by Begell House, Inc.