Osteoarthritis (OA) is a heterogeneous disease with varying degrees of inflammatory responses, structural changes, functional insufficiency, and disease progression as a whole. Some OA phenotypes are characterized by a high local inflammatory response, persistent pain, persistent synovitis, and severe functional limitation. As a rule, the use of traditional nonsteroidal anti-inflammatory drugs in these patients and the injection of glucocorticoids into the joint show no substantial effect. Taking into account the important role of inflammation and the involvement of immune responses in the pathogenesis of OA, the existence of its erosive forms, the use of some disease-modifying anti-rheumatic drugs could be a rational solution of the problem in the therapy of this disease.The paper reviews data on the efficiency and safety of using methotrexate and hydroxychloroquine in OA.