Palmitoylethanolamide, also known as PEA, is an endogenous fatty acid amide that has been demonstrated to exert a great variety of biological functions related to chronic pain and inflammation. Additionally, it has been shown to have anti-nociceptive, neuroprotective, and anticonvulsant properties. Indications for anti-inflammation and analgesia use dated as far back as before 1980. The birth of the molecule was in 1957 and it was in that year that 5 researchers believed that PEA was a natural anti-inflammatory agent. Later, in 1975, Czech physicians used PEA in a joint pain study where they found the analgesic actions to be comparable to that of Aspirin. Since then, PEA has been studied in a number of clinical trials for a variety of inflammations and pain states. Clinical opinions seem to show the most promising indications for chronic pain including diabetic neuropathy, sciatic pain, CRPS, pelvic pain and entrapment neuropathic pain states.