Cyclo-oxygenase-2 (COX-2) inhibitors have proved to be highly effective therapy for rheumatoid arthritis and, arguably, advantageous compared to traditional non-steroidal anti-inflammatory drugs (NSAIDS). The inducible nature of COX-2 has been proposed as an explanation for the high clinical efficacy of COX-2 inhibitors in inflammatory diseases. More recently, the mammalian endo-cannabinoids have been demonstrated as substrates for COX-2 but not COX-1. The resultant neutral prostaglandin (PG) biosynthetic products appear to be pharmacologically unique. Specifically, prostaglandin F_2α-ethanolamide (prostamide F_2α) and prostaglandin E₂-glyceryl ester (PGE₂-glyceryl ester) have been the subject of recent pharmacological investigation and their effects appear unrelated to interaction with known prostanoid receptors. It is possible that attenuated neutral PG formation may contribute to the beneficial effects of COX-2 inhibitors. This will be determined by future research. In terms of current therapeutics, a prostamide F_2α analog has already been approved for treating glaucoma and is extremely effective. Further therapeutic applications may be identified as the biology of neutral prostanoids is gradually elucidated.