There is a great need for alternative experimental methods for measuring percutaneous xenobiotic biotransformation. Animal testing and excised human skin studies have been the historical standards for confirmation of therapeutic and toxic effects that occur in the skin as a result of drug and other chemical metabolism. Human skin epidermal bioequivalents have become progressively more used for these types of pharmacological/toxicological studies in recent years. These epidermal models have been used in the form of cell culture, tissue sheets, and highly differentiated epidermal and epidermal/dermal systems. This review highlights the existing published data on the utility of these skin bioequivalent models for various types of metabolism and toxicology studies that should be of interest to the dermatopharmaceutical scientist.