After languishing for decades from legal restrictions and stigma, research into psychedelic drugs is exploding – with the encouragement of the Food and Drug Administration. Recent clinical trial successes suggest some long-banned drugs could soon be authorized as treatments for debilitating illnesses. Yet because of these drugs’ history, FDA approval would be just one important step in a complex process to transform these compounds into therapies. Incorporating psychedelic drugs into clinical practice will require peeling back multiple layers of legal prohibition, clarifying prescribing guidelines, and developing treatment models that work for drug-makers, physicians, and payers.