As interest in psychedelics as treatments for psychological problems grows, it is important for psychoanalysts to learn about them. Our patients will come to us to discuss their psychedelic experiences; additionally, psychedelics deserve reconsideration as meaningful collaborators with our field, at both the theoretical and clinical levels. After a brief history of these agents, the paper engages three specific areas: 1) psychedelics’ capacity to evoke egolysis, or ego dissolution, and mystical states; 2) their capacity to support hyperassociative states, free association, and emergence of unconscious material, and 3) the role of set and setting in psychedelic therapy. Drawing from the fields of neuropsychoanalysis, phenomenological research and neuroanthropology, the paper offers a discourse that connects mind and brain and psychedelics in ways meaningful for psychoanalysts.