The pathogenesis of osteoarthritis involves multiple etiologies, including mechanical, biochemical, and genetic factors that contribute to the imbalance in the synthesis and destruction of articular cartilage. It is now well documented that interleukin-1 and tumor necrosis factor-alpha are the predominant proinflammatory and catabolic cytokines involved in disease initiation and progression. Other proinflammatory cytokines may amplify or modulate this process, whereas anti-inflammatory cytokines, which are often detected, paradoxically, in osteoarthritis tissues, may counteract the tissue destruction and inflammation. This review focuses on the role of cytokines in the pathogenesis of osteoarthritis with special emphasis on how findings in culture and animal models may be reflected in the human disease process.