Per- and polyfluoroalkyl substances (PFAS) have been gaining global public and regulatory attention for several years. Their widespread use across various sectors, coupled with mounting research on their inherent persistent, bioaccumulative, and/or toxic properties, has prompted action to significantly decrease or eliminate PFAS manufacture and use. This article provides detailed analyses of the key global regulatory instruments that have shaped and may shape the future of PFAS use in our society. It details the European Union’s (EU) approaches with those adopted in the United States of America (USA) (at federal and state levels) with a focus on a comparative evaluation of the regulatory regimes and initiatives. The current outlook and impact of the Stockholm Convention on Persistent Organic Pollutants are also discussed in this article. This report informs on the future of PFAS regulation, and how pending legislation might shape the commercial and industrial markets.