Osteoarthritis (OA) remains a prevalent and difficult to treat entity, mostly due to its different phenotypes. Varying constellations of mechanic, metabolic and extrinsic factors such as trauma are main drivers of OA. Anti-inflammatory therapy by anti-interleukin 1 did not show a clear effect neither in hand or knee OA whilst it seem to reduce joint replacement at least in a certain patient populations. Corticosteroids did reduce pain and methotrexate reduced structural progression in recent hand OA trials. More promising for mechanical knee OA are growth factors such as sprifermin or kartogenin which foster the differentiation of chondrocytes. New data are available on joint safety of the subcutaneously administered anti-nerve growth factor (NGF) molecule tanezumab. In OA treatment, pain, structure, and biomechanic impairment need to be addressed.