Over the past decade, psychedelic compounds have emerged as potentially transformative therapeutics for a variety of intractable neuropsychiatric conditions. However, historically most of the basic science has utilized these compounds as probes to interrogate various endogenous neurotransmitter systems-mainly the serotonin 5-HT receptor. With the renewed interest in utilizing these compounds as therapeutics and the explosion in clinical trials, psychedelics have been purported to treat many neuropsychiatric disorders, including depression, cluster headaches, migraines, anxiety, and obsessive-compulsive disorder. It is therefore imperative to understand the biology and pharmacology behind their therapeutic mechanisms as well as expose any potential pitfalls in their widespread use as treatments. This review covers the latest advances in understanding the biological mechanisms, the newest efforts in drug discovery, and potential pitfalls when it comes to utilizing this class of compounds as emerging therapeutics.