Elevated levels of markers of nitric oxide (NO) production are found in osteoarthritic joints suggesting that NO is involved in the pathogenesis of osteoarthritis (OA). In OA, NO mediates many of the destructive effects of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) in the cartilage, and inhibitors of NO synthesis have demonstrated retardation of clinical and histological signs and symptoms in experimentally induced OA and other forms of arthritis. As an important factor in cartilage, the regulation of inducible nitric oxide synthase (iNOS) expression and activity, and the effects of NO are reviewed, especially in relation to the pathogenesis of OA.