Generous use of NSAIDs for arthritis is limited by their gastrointestinal toxicity. Identification of a second form of cyclooxygenase (COX-2), and of the association of the gastrointestinal toxicity to COX-1, generated a hope for safer anti-inflammatory agents via selective COX-2 inhibition. Consequently, rofecoxib and celecoxib were introduced in 1999, and their advantage of gastrointestinal safety over NSAIDs was demonstrated. However, selective COX-2 inhibitors (coxibs) may reduce prostacyclin production without affecting thromboxane-A2 production, thus potentially leading to an increased cardiovascular disease (CVD) risk. Mukherjee et al undertook a systematic review on CVD risks of coxibs compared with that of NSAIDs.