Depression continues as a major unmet medical need in the US and globally. However, the majority of these patients do not receive adequate improvement from currently available medications – with only a third of patients with major depression receiving a full response to a first antidepressant and a third who fail to adequately respond to multiple medications given either concurrently or sequentially. Those who do respond to medication often lose the effect over time or develop side effects that impair quality of life, and when patients discontinue these medications, they are at very high risk of having the symptoms of depression return. In addition to these disappointing outcomes, mental health-related costs are a substantial impact on our economic system and society. Psychedelic therapies have the potential to change our current approach to mental health care. Current research suggests that new treatments, such as psilocybin, could have a significant and positive impact on major depressive disorder. And follow-up studies after therapy have also shown lasting benefits. In this session, we will draw on the latest developments in clinical research to prompt the audience to consider key questions, challenges, and opportunities as we move into a new era of mental health treatment with psychedelic therapies in treatment of depression.