Diabetes mellitus is a disease of uncontrolled hyperglycemia. Despite a more sophisticated understanding of the pathophysiology of diabetes mellitus and despite pharmacologic advancements that enable better glycemic control, the prevalence of this disease and its devastating sequelae continue to rise. The adverse effects of diabetes on the nervous, vascular, and immune systems render the musculoskeletal system vulnerable to considerable damage. Foot involvement has traditionally been thought of as the most severe and frequently encountered orthopaedic consequence. However, the upper extremity, spine, and muscles are also commonly affected. Orthopaedic surgeons are more involved than ever in the care of patients with diabetes mellitus, and they play a vital role in the multidisciplinary approach used to treat these patients. As a result, surgeons must have a comprehensive understanding of the musculoskeletal manifestations and perioperative considerations of diabetes in order to most effectively care for patients with diabetes mellitus.