Overcoming PFAS analytical challenges is critical for a comprehensive understanding of PFAS toxicities and environmental impacts. This article delves into the proper development and validation of analytical methods which will allow researchers to increase throughput and decrease sources of contamination, while reducing runtimes. Included are a review of challenges related to PFAS analysis and suggestions on how to overcome them, current regulations which have been enacted to surveil PFAS exposure in environmental matrices, including U.S. EPA Method 537.1, U.S. EPA Method 1633 and EU Directive 2020/2184, and a summary of important developments including toxicity assessments for GenX and additional PFAS, the identification of new PFAS categories and innovations in method development.