Despite the multifactorial nature of musculoskeletal disease, obesity consistently emerges as a key and potentially modifiable risk factor in the onset and progression of musculoskeletal conditions of the hip, knee, ankle, foot and shoulder. To date, the majority of research has focused on the impact of obesity on bone and joint disorders, such as the risk of fracture and osteoarthritis. However, emerging evidence indicates that obesity may also have a profound effect on soft-tissue structures, such as tendon, fascia and cartilage. Although the mechanism remains unclear, the functional and structural limitations imposed by the additional loading of the locomotor system in obesity have been almost universally accepted to produce aberrant mechanics during locomotor tasks, thereby unduly raising stress within connective-tissue structures and the potential for musculoskeletal injury. While such mechanical theories abound, there is surprisingly little scientific evidence directly linking musculoskeletal injury to altered biomechanics in the obese. For the most part, even the biomechanical effects of obesity on the locomotor system remain unknown. Given the global increase in obesity and the rapid rise in musculoskeletal disorders, there is a need to determine the physical consequences of continued repetitive loading of major structures of the locomotor system in the obese and to establish how obesity may interact with other factors to potentially increase the risk of musculoskeletal disease.