Cyclic prostanoids play important physiologic roles in inflammation and maintaining normal function of several organ systems. Prostaglandin production requires the conversion of arachidonate to the intermediate prostaglandin H2, by the 2-step cyclo-oxygenation and peroxidation catalyzed by the enzyme cyclo-oxygenase (also called prostaglandin H synthase). Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) block the production of cyclic prostanoids by binding in different ways to this enzyme and blocking the active site. This results in decreased inflammation, but it can also produce side effects in the gastrointestinal tract, kidney, and platelets. Recent data demonstrate that there are 2 isoforms of the cyclo-oxygenase enzyme, called COX-1 and COX-2. These isoforms are similar in size, substrate specificity, and kinetics, but vary in their expression and distribution. Normal physiologic functions appear to be maintained by COX-1, while COX-2 appears to mediate the inflammatory response. Nonsteroidal drugs with selective inhibitory activity on the COX-2 isoform should theoretically decrease inflammation while maintaining normal physiologic prostaglandin levels. Current NSAIDs are not selective enough to confirm this, but newer, more selective inhibitors of COX-2 may answer this important question.