To describe recent developments highlighting the effects and mechanisms of obesity and weight loss on the musculoskeletal system.The global epidemic of obesity has far-reaching effects on the musculoskeletal system and associated conditions such as osteoarthritis, rheumatoid arthritis, spondyloarthropathy, and fibromyalgia. Obesity increases the need for, and reduces the health outcomes from, joint replacement surgery, which has enormous implications for societal economic burden. New insights have been gained into the possible mechanisms by which obesity is associated with musculoskeletal disease incidence, symptom severity and treatment outcomes particularly for osteoarthritis. Research exploring the role of adipocytokines provides a novel possible metabolic link for these diseases.Obesity has a significant impact on the musculoskeletal system being associated with both degenerative and inflammatory conditions. Future research assessing the effects of obesity and weight loss as well as further elucidating the action of adipocytokines will aid in the assessment and management of this increasingly prevalent condition.