Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. It is an inexpensive and useful medication, with a low incidence of adverse drug events. Nonetheless, optimal clinical outcomes require that a series of screening and laboratory steps be followed before the initiation of VPA therapy. An additional aspect of pharmacovigilance is to recognize clinical patterns signaling genetic traits that preclude VPA, background of the black box warnings, targeted assessments, and laboratory monitoring indicated while on VPA. The intention of this article is to provide a focused summary of published information clinically relevant to prescribing and monitoring these patients.