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Humans have been using nonsteroid antiinf lammatory drugs (NSAIDs) in various forms for more than 3,500 years (1). They are still our favorite medicines. Estimates vary, but it appears, for instance, that each year we consume around 40,000 metric tons of aspirin, equating to about 120 billion aspirin tablets (300 mg is a standard size). In addition, dozens of other NSAIDs and NSAID formulations are available and enthusiastically consumed in most countries. However, despite this long history and large volume of use, we still have an incomplete understanding of how the NSAIDs achieve their actions. Most recently, molecular biology, together with pharmacology, has brought the greatest steps forward in knowledge. It is in this vein that Dan Simmon’s group report the discovery of a novel cyclooxygenase (COX) enzyme variant that could be the target of acetaminophen and other analgesicantipyretic drugs (2). After 3 …