The growing awareness of per- and polyfluoroalkyl substances (PFAS) in drinking water throughout the U.S is driving the demand for technically defendable, risk-based drinking water standards. In May 2016, the U.S. Environmental Protection Agency (EPA) issued lifetime health advisory levels of 70 parts per trillion (ppt) individually or for the sum of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), as guidance. In February 2019, the EPA decided to move forward with the development of a PFOA and PFOS maximum contaminant level (MCL) process as part of their National PFAS Action Plan under the Safe Drinking Water Act. In the absence of federally-developed enforceable standards, individual states are using their authority to develop and enforce drinking water standards and guidelines. This has resulted in a wide variation of PFAS drinking water guidelines and standards across state and federal agencies. This variation is related to limited and developing knowledge regarding the critical health effects associated with PFAS exposure over time and largely reflects discordant risk assessment principles and practices among the regulatory agencies.