Per- and polyfluoroalkyl substances (PFAS) are a family of fluorinated organic compounds of anthropogenic origin. Due to their unique chemical properties, widespread production, environmental distribution, long-term persistence, bioaccumulative potential, and associated risks for human health, PFAS have been classified as persistent organic pollutants of significant concern. Scientific evidence from the last several decades suggests that their widespread occurrence in the environment correlates with adverse effects on human health and ecology. The presence of PFAS in the aquatic environment demonstrates a close link between the anthroposphere and the hydrological cycle, and concentrations of PFAS in surface and groundwater range in value along the ng L−1–μg L−1scale. Here, we critically reviewed the research published in the last decade on the global occurrence and distribution of PFAS in the aquatic environment. Ours is the first paper to critically evaluate the occurrence of PFAS at the continental scale and the evolving global regulatory responses to manage and mitigate the adverse human health risks posed by PFAS. The review reports that PFAS are widespread despite being phased out—they have been detected in different continents irrespective of the level of industrial development. Their occurrence far from the potential sources suggests that long-range atmospheric transport is an important pathway of PFAS distribution. Recently, several studies have investigated the health impacts of PFAS exposure—they have been detected in biota, drinking water, food, air, and human serum. In response to the emerging information about PFAS toxicity, several countries have provided administrative guidelines for PFAS in water, including Canada, the United Kingdom, Sweden, Norway, Germany, and Australia. In the US, additional regulatory measures are under consideration. Further, many PFAS have now been listed as persistent organic pollutants. This comprehensive review provides crucial baseline information on the global occurrence, distribution, and regulatory framework of PFAS.