Herbal and dietary supplements (HDS) are commonly used in the United States and throughout the world. The Dietary Supplement Health and Education Act and public standards set through the U.S. Pharmacopeia provide regulatory framework for these products. These regulations help to ensure the safety of grandfathered and new HDS coming onto the market, and the opportunity to identify and take action against unsafe products that have been distributed. The clinical patterns of presentation and severity of HDS-associated hepatotoxicity can be highly variable, even for the same product. In addition, accurate causality assessment in cases of suspected HDS hepatotoxicity is confounded by infrequent ascertainment of product intake by healthcare providers, under-reporting of HDS use by patients, the ubiquity of HDS and the complexity of their components, and the possibility for product adulteration. Additional measures to prevent HDS-induced hepatotoxicity include greater consumer and provider awareness, increased spontaneous reporting, and reassessment of regulations regarding the manufacturing, distribution, and marketing of these products.