The combined stability, mobility, and bioaccumulation of per- and poly-fluoroalkyl substances (PFAS) has prompted a global environmental crisis. PFAS have unique properties owing to their strong, hydrophobic C–F bonds, which result in their resistance to water, oil, chemicals, and heat. Applications of PFAS include their use as water-, grease-, and fire-proof coatings, emulsifiers, and surfactants, spanning most manufacturing sectors. The continued regulation of specific PFAS provides significant research opportunities for chemists and their collaborators across environmental, social, engineering, and materials sciences. Solutions in the areas of detection and analysis, immobilisation and destruction, and the creation of viable and safe alternatives are urgently needed. In this tutorial review, PFAS and their associated challenges are described, followed by a summary of existing solutions and future research opportunities.