The recalcitrant behavior of per- and polyfluoroalkyl substances (PFAS) to most traditional water treatment processes is driving the development of new or modified treatment approaches for PFAS destruction. This paper evaluates and compares the strengths and limitations of available physico-chemical treatment techniques. A comparative assessment based on effectiveness (extent of degradation and defluorination) and efficiency (rate, cost, and energy use) revealed that electrochemical oxidation, advanced reduction processes (ARPs) and plasma-based technology exhibited the best potential towards overall process efficiency. Sonolysis and heat-activated persulfate had the highest energy demand while photochemical oxidation was the most ineffective method.