The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Agency (EPA) establish standards for 83 contaminants by June 1989, and at least 25 added standards by January 1991, then 25 more every three years hence. Conceptually, the regulatory process employed by EPA consists of two steps. First, a detailed health risk assessment of a contaminant is performed in order to determine the Maximum Contaminant Level Goal (nonenforceable health goal) in water that should result in no known or anticipated health effects and allows adequate margin of safety. Second, the results of risk assessment and management (taking best available technology, treatment techniques, cost, and other means into consideration) are combined to derive the Maximum Contaminant Level (enforceable standard) which is set as close to the MCLG as feasible. With this overall regulatory process in mind, a detailed risk assessment process (hazard identification, dose-response assessment, human exposure assessment, and risk characterization) used in setting drinking water standards is discussed. In addition, this article discusses our efforts in exploring new and improved risk assessment methodologies addressing the mechanism of action of toxicants, relative source contribution, weight of evidence, carcinogenic potency, and toxicokinetics.