Isotretinoin is a synthetic oral retinoid that has great efficacy against severe, recalcitrant, nodulocystic acne. Since its introduction to the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behavior, suicide, and suicide attempts. A MEDLINE review was performed to compile all case reports, case series, adverse drug event reportings, and prospective and retrospective studies relating psychiatric adverse events to isotretinoin. In addition, literature linking a biological mechanism for psychiatric adverse events to retinoid signaling pathways was also reviewed. Although a variety of anecdotal and epidemiologic studies are available, the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between istotretinoin and psychiatric adverse events. Several lines of evidence link retinoid signaling to theorized psychiatric pathogenesis, but are limited in their applicability to adult neurophysiology.