Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX) -2 inhibitors with the potential to reduce the risk of gastrointestinal bleeding, have their crucial role in the control of inflammation. However, they have recently been shown to have a preventing effect against joint destruction by basic studies related to pathophysiology in rheumatoid arthritis. Here we summarize the current knowledge on anti-proliferative action due to apoptosis, suppression of angiogenesis, and suppression of osteoclastic bone resorption by NSAIDs. COX-2-dependent and/or -independent mechanisms for these actions have been suggested. Several NSAIDs including selective COX-2 inhibitors have been suggested to possess the in vivo preventing effects on joint destruction in animal models of rheumatoid arthritis. However, clinical evidence on the disease modifying effects of COX-2 inhibitors in patients with rheumatoid arthritis remains to be studied.