For more than 20 years, the mainstay of pharmacologic treatment for depression and anxiety disorders has been serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors. There are newer medications, many with novel mechanisms of action, that have come to market; however, first-line treatments remain the same. There are now more robust data on the use of various augmentation agents in the treatment of major depressive disorder providing better recommendations for use by the primary care provider. Data to support the use of psychedelic-assisted psychotherapy in the treatment of mood and anxiety disorders are not robust enough to recommend generalized use at this time.