Psilocybin is a psychoactive alkaloid that is produced naturally by approximately 200 species of mushrooms. 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 biosynthetic 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.