Background and aims Set and setting function both as a concept that guides research and practice with psychedelic drugs and as a meme aimed at reducing harm among psychedelic users. Referring to non-pharmacological factors that shape drug experiences, the concept of set and setting was popularized in the West during the mid-20th century. However, little theoretical development has occurred regarding what falls under the umbrella of set and setting since its conception. Methods By bridging set and setting theory with research from the fields of social psychology and sociology of medicine, this review calls attention to how race can contribute the set and setting for a psychedelic experience. Results I argue that psychosocial factors influencing racial differences in mental health also constitute meaningful differences in set. Furthermore, I suggest that the character of race relations in the United States provides a distinct cultural setting for racialized psychedelic users, both in therapeutic and naturalistic contexts. In turn, racial identification may contribute to the variation in framing and interpretation of psychedelic experiences. Conclusion These considerations have important implications beyond understanding non-pharmacological influences on psychedelic experiences, including developing protocols for clinical applications of psychedelics, educating future practitioners, and meeting the needs of diverse patient populations.