The cyclooxygenase (COX)-2–selective nonsteroidal anti-inflammatory drugs (NSAIDs; coxibs) were developed in order to reduce upper gastrointestinal (GI) side effects associated with traditional nonselective NSAIDs. This article presents an overview of clinical trials showing the efficacy of coxibs for the treatment of patients with arthritis. In osteoarthritis trials, coxibs were more effective than placebo and similarly effective compared with standard doses of traditional NSAIDs. Some studies lasted up to a year and showed effectiveness of coxibs for long-term treatment of patients with osteoarthritis. There are currently few adequately powered trials comparing the efficacy of the 2 first-generation coxibs, celecoxib and rofecoxib. Of 2 head-to-head studies comparing the 2 agents, 1 indicated similar efficacy, whereas the other showed the superiority of rofecoxib at a dose of 25 mg daily compared with celecoxib at a dose of 200 mg daily. In studies enrolling patients with rheumatoid arthritis, coxibs also have shown efficacy superior to that of placebo and similar to that of traditional NSAIDs. There are no clinical trials comparing the efficacy of different coxibs for treatment of patients with rheumatoid arthritis. In endoscopic studies, the GI safety and tolerability profile of coxibs has been consistently superior to that of traditional NSAIDs. In large clinical outcome trials, at least 1 of the coxibs, rofecoxib, significantly reduced the risk of confirmed complicated upper GI events compared with the conventional NSAID naproxen. Both rofecoxib and celecoxib reduced the risk of confirmed clinical upper GI events compared with the nonselective NSAIDs naproxen and ibuprofen in patients with osteoarthritis and rheumatoid arthritis not taking low-dose aspirin. Therefore, coxibs provide effective relief of pain from osteoarthritis and rheumatoid arthritis, with efficacy that is comparable to traditional NSAIDs, but with a significantly lower incidence of GI complications. Semin Arthritis Rheum 32(Suppl 1):4-14. Copyright 2002, Elsevier Science (USA). All rights reserved.