Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression; the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA; however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and amplification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA.