Cytokines help mediate the acute and chronic inflammation and associated destruction of connective tissue in arthritic temporomandibular joints (TMJ). The proinflammatory cytokines TNFα, IL-1β, IL-6, IL-8, and IFN-γ are associated with inflammation in synovial joints and connective tissue destruction. Therefore, the increased levels of these cytokines in the synovial fluid of temporomandibular disorder (TMD) patients would be expected. Conversely, IL-1ra and IL-10 acts as inhibitors to these proinflammatory cytokines. Thus, in TMD patients, low levels of IL-1ra and IL-10 might be expected. A review of studies from multiple investigators confirms that proinflammatory cytokine levels increase in TMD patients, IL-1ra levels are also increased, and IL-10 levels remain unchanged. Because IL-10 can inhibit TNFα, IL-1, IL-6, and IL-8, the lack of IL-10 in the TMJ in the face of the other studies showing increases in TNFα, IL-1β, IL-6, and IL-8 could partially explain the exacerbation of the associated osteoarthritis. In addition, although IL-1ra levels are elevated in most of the TMD patients, the increases do not appear to be sufficient to inhibit the inflammation and connective tissue degradation associated with IL-1β. Thus, it appears that treatment of TMD requires a delicate balance between proinflammatory cytokines and cytokine inhibitors such as IL-1ra and IL-10.