OA is a complex disease involving mechanical, metabolic and inflammatory contributions to its aetiology. A key risk factor, obesity, is becoming an increasing focus of research due to its multiple potential impacts on OA incidence, progression and symptom severity. An increased load due to an increase in body mass has been well established as a mechanical contribution to the pathophysiology of OA. However, evidence of obesity-linked to OA in non-weight-bearing joints has implicated the biological role of adipose inflammation and metabolic abnormalities in OA. The identification of inflammatory mediators such as adipokines (adipose-derived molecules) in OA has further incriminated the role of adiposity. This narrative review aims to discuss the role of adipose-derived inflammation in OA, with a focus on the contrast between systemic and local adipose tissue, and potential treatment applications targeting the adipo-inflammatory aspects of the disease.