Rationale: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for mental health conditions, such as substance use disorders and depression. The current model for PAP emphasizes the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical study concerning the “psychotherapy” in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. Objectives: As clinical trials for psychedelic compounds begin the transition from demonstrating safety and feasibility to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and ensure safety.Results: The present paper first reviews the current status of psychotherapy in the PAP literature, overviewing both published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments, identifying mechanisms of change, and optimizing clinical trial designs. Throughout this review, we underscore the need for increased research on the psychotherapeutic component of treatment in PAP. Conclusions: PAP is a highly unique and transdisciplinary intervention, and future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.