Metabolic syndrome-associated osteoarthritis (Met-OA) is a clinical phenotype defined by the role of obesity and metabolic syndrome as risk factors and by chronic low-grade inflammation. Obesity is an established risk factor for osteoarthritis not only at the knee, but also at the hands. Metabolic syndrome is also a risk factor for osteoarthritis, and a cumulative effect of the various syndrome components combines with an independent effect of each individual component (diabetes, dyslipidemia, and/or hypertension). The higher incidence of osteoarthritis in patients with obesity is related to several factors. One is the larger fat mass, which imposes heavier loads on the joints. Another is endocrine production by the adipose tissue of proinflammatory mediators (cytokines, adipokines, fatty acids, and reactive oxygen species) that adversely affect joint tissues. Obesity-related dysbiosis and sarcopenia were more recently implicated in the association between obesity and osteoarthritis. Finally, patients who have osteoarthritis, with or without metabolic syndrome, are at increased risk for cardiovascular mortality due not only to a sedentary lifestyle, but also to shared risk factors. Among these is the low-grade inflammation seen in patients with metabolic disorders. Thus, primary prevention and appropriate management of obesity and metabolic syndrome may delay the development and slow the progression of osteoarthritis.