Osteoarthritis (OA) is a major cause of pain and is characterized by loss of articular cartilage integrity, synovitis and remodeling of subchondral bone. However, OA pain mechanisms remain incompletely understood. Pain severity does not always correlate with the extent of joint damage. Furthermore, many people with OA continue to experience pain despite optimal use of standard therapies that target the joints, including joint-replacement surgery. There is compelling evidence that altered central pain processing plays an important role in maintaining pain and increasing pain severity in some people with OA. A key challenge is to identify this subgroup of patients with abnormal central pain processing in order to improve their clinical outcomes by developing and targeting specific analgesic treatments.