Osteoarthritis (OA) is a slowly progressive degenerative disease characterized by gradual loss of articular cartilage. Since the OA lesion is often localized to weight-bearing cartilage or to sites of trauma, repetitive mechanical injury has been proposed as the critical signal for the initiation and progression of OA. It is now generally accepted that the chondrocyte is the target of these abnormal biomechanical factors, and that biochemical and genetic factors also contribute to alterations in the normal functional activities of these cells. Although OA has been regarded primarily as a noninflammatory arthropathy, symptoms of local inflammation and synovitis are present in many patients and have been observed in animal models of OA. Even in the absence of classic inflammation, which is characterized by infiltration of neutrophils and macrophages into joint tissues, elevated levels of inflammatory cytokines have been measured in OA synovial fluid. Although the OA cartilage lesion is present at sites remote from the synovium, the fibroblast-and macrophage-like synovial cells, as well as the chondrocyte itself, are potential sources of cytokines that could induce chondrocytes to synthesize and secrete cartilagedegrading proteases, cytokines, and other inflammatory mediators. These synovium-and chondrocyte-derived products represent potential targets for the development of therapeutic agents, such as proteinase inhibitors, cytokine antagonists, and cytokine receptor blocking antibodies, which could be used to prevent or retard the progression of the OA articular lesion. This review will focus on evidence that implicates chondrocyte responses to cytokines in the pathogenesis of OA and will discuss the potential therapeutic applications of these findings.