In addition to physical symptoms and treatment burden, people affected by serious illness experience psychological, social, and spiritual distress. Medical professionals who care for them, including psychiatrists and other mental health clinicians, attend to these multiple dimensions of suffering with the hope and promise of improving patients' quality of life. Yet anxiety, depression, adjustment disorder, and existential distress often prove resistant to existing medical or behavioral interventions. A growing body of evidence suggests the safety and efficacy of psychedelic-assisted therapies (PATs) to improve these outcomes. As societal norms around the stigma of psychedelic agents shift, there is an increasing interest in integrating these treatment modalities into serious illness care. To promote awareness among mental health professionals, this article describes aspects of serious illness care that might be amenable to PATs, reviews the evidence documenting the safety and efficacy of PATs in serious illness care, and highlights some of the opportunities and challenges moving forward. [ Psychiatr Ann. 2022;52(9):359–364.]

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