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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used in the treatment of pain, including pain of dental origin, for many years. Even though they are effective in relieving symptoms, they are not without adverse events, most notably upper gastrointestinal toxicity.To prevent this side effect, the pharmaceutical industry developed NSAIDs that selectively inhibit the cyclooxygenase 2 (COX-2) isoenzyme, which is inducible and expressed at sites of inflammation, while sparing the COX-1 isoenzyme, which is associated with gastric protection. On September 30, 2004, the company that produced rofecoxib (Vioxx), a COX-2 inhibitor, voluntarily withdrew this product from the market based on the discovery of its association with increased risk of adverse cardiovascular events reported in an ongoing large clinical trial. This unexpected event caused the medical community to review existing literature regarding this and related medications and also led to the emergence of novel research to improve understanding of the potential mechanisms for this serious side effect. However, instead of clarifying the situation, reports created confusion and controversy regarding the safety of all types of NSAIDs.The major concern is an increase in adverse cardiovascular events with the use of individual drugs as well as the potential for a class effect. In this article, we review recent events and findings and discuss the implications for dentistry.