Obsessive-compulsive disorder (OCD) is a highly prevalent and disabling condition for which currently available treatments are insufficiently effective and alternatives merit priority attention. Psilocybin may represent a safe and effective avenue for treatment of individuals affected by this condition. In this chapter we briefly introduce OCD symptoms, epidemiology, as well as relevant hypotheses on the mechanism of disease that may inform treatment interventions. We briefly describe currently available treatments, mechanisms of action, and efficacy limitations, as preamble to the potential use of psilocybin and perhaps similar compounds in the treatment of OCD and related conditions. Although much is reviewed throughout this book about the mechanisms of action of psychedelic agents, a focused discussion of psilocybin effects as they pertain to OCD is also included. Our experience with incidental observation, prospective research, and current explorations of psilocybin in OCD are also described.