The specific causative agent of the pathological process of osteoarthritis (OA) has not yet been identified, however, episodic inflammation at the clinical stage is now a well documented phenomenon and believed to be involved in the disease progression. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are the predominant proinflammatory cytokines synthesized during the OA process. Other cytokines having proinflammatory properties or catabolic factors could also contribute to this pathological condition, and those having antiinflammatory properties may be able to counteract the negative effects of the former on the disease process. In this chapter, we will review cytokine interactions and their modulatory effects on joint articular tissue metabolism, including their stimulatory and/or inhibitory actions, and their potential relevance to OA. We will also briefly survey the major biological factors, in relation to cytokines, that look promising for future therapeutic approaches.