Osteoarthritis (OA) results from joint pathology that is clinically associated with pain. It may be the shared end result of various initiating factors, including trauma or immune-mediated inflammation. Historically, OA has been labeled as a ‘non-inflammatory arthritis’ or as a ‘wear-and-tear disease’. From a pathogenesis standpoint, these labels represent half-truths. Inflammatory mediators play a critical role in pathological processes across the joint, even though inflammation might be less pronounced in OA than in rheumatoid arthritis.