As quickly as our understanding of the nature and extent of per‐ and polyfluoroalkyl substances (PFAS) in the environment has developed, the analytical chemistry tools we use to study and quantify them have evolved. The last 5 years have seen commercial laboratories scramble to analyze atypical and unusual samples submitted by concerned citizens and governmental agencies. The unusual matrices have pushed innovative sample extraction techniques, as the regulated community and the laboratories await a final multilaboratory validated method to provide direction for the analysis of PFAS in matrices beyond drinking water. The large number of PFAS compounds has also sparked interest in the development of methods to screen for all PFAS without quantifying the individual constituents. Measurement of total PFAS is also useful in consumer product testing.

New methods to determine total PFAS are in varying stages of development and are described in detail herein. The fact that there are more PFAS chemicals than can be quantified by commercial laboratories has also promoted the development of nontarget analysis (NTA) using sophisticated instrumentation. This article provides the basis of NTA and examples of its novel applications in forensics and compound identification. The pace of change in PFAS analysis is breathtaking and challenging for all those studying environmental impacts of PFAS. Updates on key topics as can be found in this article serve an important need for the remediation community.