This digital supplement explores the analytical hurdles laboratories face as PFAS testing pushes into trace-level territory, from a chemical universe spanning millions of structures to persistent background contamination and non-harmonized methods across regulatory bodies. Featured research covers non-targeted screening strategies for identifying unsuspected PFAS in complex food matrices, advanced multisorbent extraction and mass spectrometry workflows for organofluorines in municipal wastewater, and findings that PFAS concentrations in estuaries can shift four- to sevenfold within a single tidal cycle. Additional coverage details the development of fluorinated SPME sorbents for selective extraction of volatile PFAS and a fast GC-MS/MS method capable of detecting 37 PFAS compounds in food packaging in just 8 minutes. Together, these articles offer a data-driven look at emerging tools and techniques designed to keep pace with PFAS's expanding chemical scope and evolving regulatory demands.