Osteonecrosis is one of the most devastating musculoskeletal manifestations of sickle cell disease and most commonly affects the femoral head. Although the exact pathophysiology of this condition in patients with sickle cell disease is unknown, it is suggested that red cell sickling and repetitive vaso-occlusion may be associated with tissue hypoxia, inflammation, and subsequent bone necrosis and collapse. If left untreated, osteonecrosis can be extremely debilitating and may lead to severe pain, loss of function, and degenerative joint changes. Although several conservative management approaches exist, total joint arthroplasty remains the most effective treatment intervention. A multidisciplinary approach among the primary care physician, hematologist, and orthopedic surgeon is essential in optimizing patient management.