Cyclooxygenase-2 (cox-2) inhibitors, also known as coxibs, were introduced with the promise that they would provide pain relief similar to that of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) but would be better tolerated with lower risk of gastrointestinal (GI) side effects. Although coxibs were associated with lower GI risk, experimental and observational data raised the specter of increased cardiovascular risk associated with this class of drugs. This article describes the pharmacologic and biologic basis of cardiovascular risk associated with coxibs, summarizes the evidence for cardiovascular risk associated with cox-2 inhibitors, and weighs the risks and potential benefits of pain management with these agents.