Nonsteroidal anti-inflammatory drugs (NSAIDs), both nonselective and cyclooxygenase-2-specific inhibitors, are commonly used medications for the relief of acute and chronic pain associated with a wide range of medical conditions. Because of the extensive use of these agents, adverse events that occur infrequently may still affect the overall risk/benefit ratio of this class of medications. Serious adverse cardiovascular (CV) events have been reported with NSAID use, but unfortunately, definitive evidence regarding the precise CV risk associated with these drugs, as a class and individually, is lacking. Therefore, it is an issue of public health importance that physicians be guided by careful assessment of the existing evidence to make reasonable choices in prescribing these medications. The investigators review the key clinical trials, meta-analyses of clinical trials, and epidemiologic studies on the subject of the CV safety of NSAIDs and identify key variables that define the CV risk of the NSAIDs. In conclusion, it is important that cardiologists, who are not among those physicians frequently prescribing NSAIDs, have a particular responsibility to have up-to-date, thoughtfully synthesized information about the CV risks of these drugs, especially when administered to patients receiving low-dose aspirin for cardioprotection.