Two isozymes of cyclooxygenase (COX), COX-1 and COX-2 were discovered in 1991. Based upon the molecular composition of COX-1 and COX-2, selective COX-2 inhibitors such as celecoxib and rofecoxib were synthesized. The incidence of severe gastrointestinal events in patients treated with selective COX-2 inhibitors has been proven to be lower than in patients treated with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). However, there were small differences in renal complications between the two groups. In contrast, an increased incidence of cardiovascular diseases, such as myocardial infarction and cardiac failure after administration of selective COX-2 inhibitors may occur in patients with risk factors for atherosclerotic or thrombotic complications. Rofecoxib was withdrawn from the world market due to collected reports of the cardiovascular complications, while celecoxib remained because of lower concern. In addition, the population-based nested case-control analysis for the risk of myocardial infarction suggested increased cardiovascular diseases by use of all NSAIDs. Further basic and clinical studies need to be investigated in the future.