Given hundreds of natural and human-made chemical agents in water to which people around the world could be exposed, a critical issue for maintaining healthful water supplies for the future is to determine "safe" exposure levels. Regulatory guidelines designed by law to protect health and welfare have been the governmental foundation and basis for establishing safe exposure levels. For example, for noncarcinogenic or systemic effects, U.S. Environmental Protection Agency develops reference doses and the State of California develops Public Health Goals. As part of the process of setting regulatory guidelines, agencies generally incorporate scientific information about the potential for health effects or exposure. However, each agency also applies policy components that can have the unintended effect of weakening the guideline's scientific validity and transparency. This paper outlines current methods used to establish "safe" drinking water levels, and offers alternatives that incorporate current science to yield "safe" levels with improved certainty, transparency and reproducibility yet are still health protective. As an example, a method of assessing pharmaceutical agents in drinking water is presented. Includes abstract only.