Osteoarthritis, although primarily a degenerative joint disease, may be associated with significant secondary inflammation. Hydrolytic enzymes result in primary cartilage degradation; secondary inflammation occurs in response to degenerative cartilage breakdown products and crystal deposition. Humoral and cell-mediated immune responses have been described. Analgesic and anti-inflammatory agents play a major role in symptomatic relief. Anti-inflammatory activity of the nonsteroidal anti-inflammatory drugs has been ascribed to prostaglandin synthesis inhibition; recent studies suggest additional effects based on inhibition of neutrophil aggregation, superoxide radical generation, and lysosomal enzyme release. Indomethacin, the first of the newer nonsteroidal anti-inflammatory drugs, has a long history of use and patient acceptance. Sustained-release indomethacin (Indocin SR), a 75 mg formulation equivalent to three consecutive doses of conventional indomethacin, adds ease of administration and potential for improved compliance. Nonsteroidal anti-inflammatory drugs, used in conjunction with other therapeutic approaches, provide the opportunity for response that can be gratifying for both patients and physicians.