The potential of NSAIDs, including COX-2 elective drugs, to increase the risk of heart atckand stroke has become a recent worldwide concern. Indeed, this risk is now receiving more attentionthan the well characterized ability of NSAIDs to pecipitate gastric ulcers and other gastrointestinaladverse events. When selective inhibitors of COX-2 were developed, their potential to causecardiovascular side effects was no considered; the main objective was to produce drugs that retainedthe anti-inflammatory and analgesic effects of traditional NSAIDs without their gastrointestinalside effects. Newer drugs such as rofecoxib were therefore tested in animal and human tests ofNSAID efficacy and NSAID-induced gastrointestinal damage, but were not examined in modelsof cardiovascular safety. However, the latest available findings indicate that we must now extendour range of concerns about NSAID toxicity and include cardiovascular risk as an element in thedevelopment of new drugs.