The nonsteroidal antiinflammatory drugs (NSAIDs) continue to be important therapeutic interventions for the treatment of pain and inflammation. Investigators continue to produce new information about their biologic effects, including their actions as well as their toxic effects and methods to decrease the potential side effects associated with their use. This year many papers have been published speculating about those NSAIDs that are reported to selectively inhibit the isoform of the cyclooxygenase enzyme that is induced in inflammatory conditions (Cox-2) rather than that associated with normal physiologic function (Cox-1). Reports have shown that the more Cox-2-selective NSAIDs (from three- to 10-fold more selective for Cox-2 over Cox-1) seem to have less gastrointestinal toxicity associated with their use; however, little evidence has yet emerged from phase I, II, or III studies about the clinical effects of the highly selective Cox-2 inhibitors (300-fold or more selective for Cox-2 over Cox-1). In addition, intriguing animal studies have shown the effects of knockout of the genes controlling the activities of either Cox-1 or Cox-2 in mice.