One hundred years after the introduction of aspirin, greater understanding of the mechanism of action of NSAIDs has led to the development of selective COX-2 inhibitors. These have been shown to reduce pain and inflammation with reduced risk of GI complications. However, questions remain regarding such issues as restriction of their use to patients at high risk for complications, cost-effectiveness, effectiveness compared with prostaglandin replacement or acid reduction therapy, and safety in patients also taking aspirin for platelet inhibition.