Early research examined use of psychedelic drugs such as LSD in the treatment of various health conditions including for palliative care and addictions. Research in this area was largely halted in the 1970s after criminalization and due to stigma associated with widespread recreational use. The 21^st century has seen a renewed interest in this area with psychedelics such as psilocybin and ayahuasca being studied again for potential therapeutic effects in anxiety, mood, and substance use disorders. This presentation will provide a historical overview of clinical research with psychedelics and discuss recent developments in the field. Recent preliminary studies investigating mental health outcomes of psychedelic-assisted treatments will be presented and potential biological and psychological mechanisms will be described in brief.