Concomitant inhibition of both cyclooxygenase (COX) isoforms, COX-1 and COX-2, has been used to explain the therapeutic efficacy and gastrointestinal (GI) toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatic diseases. While COX-2 is induced during inflammatory responses, constitutively expressed COX-1 is cytoprotective in the GI tract. Newer inhibitors such as meloxicam, which have been shown to inhibit COX-2 preferentially in vitro, are expected to retain their efficacy while exhibiting decreased toxicity. Clinical trials have been performed with meloxicam to evaluate these parameters. Controlled trials showed that meloxicam is significantly more effective than the placebo fur the treatment of both rheumatoid arthritis and osteoarthritis. In comparative studies with piroxicam, naproxen, and diclofenac, meloxicam was approximately as effective as the other drugs. Analysis of the safety profile of meloxicam indicated that the risk of CI adverse events, especially PUBs (perforation, ulceration, and bleeding) is significantly reduced with meloxicam compared with that of the comparators. These data confirm that preferential COX-2 inhibitors such as meloxicam provide a significant advantage over standard NSAIDs in the treatment of rheumatic diseases.