Drug molecules are typically subjected to a variety of biotransformation reactions, and the metabolites formed through these reactions must be considered when conducting safety testing programs for new chemical entities. Metabolites that are chemically stable sometimes have pharmacological activity profiles similar to those of the parent compound but rarely have potent activity against off-target receptors that is unique relative to the parent profile. This fact argues for the thorough testing of drug metabolites for their pharmacological activity. It also argues for a significantly lower need for the thorough characterization and quantitation of stable metabolites not thought to substantially contribute to the pharmacodynamic effect. Given the tremendous resource requirements involved in the thorough characterization of drug metabolites, a more flexible, tiered approach to stable metabolite characterization would seem to provide the best utilization of resources while still allowing a complete evaluation of the toxicological profile of a new drug.