Psilocybin and lysergic acid diethylamide (LSD-25) are two of the most popular and well known psychedelic drugs. Although both of the compounds are currently illegal in the United States, a renewed interest has begun in recent years to examine and analyze these drugs for therapeutic use. This review analyzes the current research pertaining to the metabolism, biochemical pathways, receptor activity, biological signaling, physiological effects and the behavioral effects associated with both of these compounds. For psychedelic compounds to be used in future therapeutic settings, it is important to understand how each compound affects the body and which psychedelic could provide more effective treatment for a particular ailment. Accordingly, this review addresses the chemical biology of psilocybin and LSD-25 and provides an initial comparative framework for assessing the effectiveness of each drug under certain circumstances.