Osteoarthritis is one of the most frequent, disabling, and costly pathologies of modern society. Among the main aims of osteoarthritis management are pain control and functional ability improvement. The exact cause of osteoarthritis pain remains unclear. In addition to the pathological changes in articular structures, changes in central pain processing or central sensitization appear to be involved in osteoarthritis pain. The latter calls for a broader approach to the management of patients with osteoarthritis. Yet, the scientific literature offers scant information addressing the treatment of central sensitization, specifically in patients with osteoarthritis. Interventions such as cognitive-behavioral therapy and neuroscience education potentially target cognitive-emotional sensitization (and descending facilitation), and centrally acting drugs and exercise therapy can improve endogenous analgesia (descending inhibition) in patients with osteoarthritis. Future studies should assess these new treatment avenues.