Abstract Individuals with musculoskeletal pain exhibit abnormal movement patterns, including antalgic gait, postural dysfunction, increased thoracolumbar stiffness, decreased proprioception, and altered activation of abdominal and extensor muscles. Additionally, aberrant or increased biomechanical forces over time produce joint or structural damage that results in pain. A large body habitus resulting from excessive weight can accelerate these musculoskeletal complaints. Irrespective of age, obesity contributes to chronic musculoskeletal pain, impairment of mobility, and eventual physical disability. Potential mechanisms that may mediate the relationships between obesity-related pain and functional decline include skeletal muscle strength deterioration, systemic inflammation, and psychosocial characteristics (eg, pain catastrophizing, kinesiophobia, and depression). Treatment considerations for obese patients with musculoskeletal pain include assessment of kinesiophobia levels, biomechanical analysis, and pain medication use. Ideally, a multidisciplinary team of physicians, psychologists, and physical therapists should optimize the design of interventions specific to the patient. In some cases, the use of appropriate pain medications or intra-articular injectable agents may help control pain, fostering sustained activity, caloric expenditure, and weight loss. Morbid obesity is a medical condition that alters biomechanical forces on the tissues of the body. This condition provides the opportunity to examine accelerated development of musculoskeletal pain syndromes and etiology. The proposed therapeutic interventions can have multiple benefits in the obese population including weight loss, improved psychological outlook and self-efficacy, reduced kinesiophobia levels, reduced risk of functional dependence, and improved quality of life.