Sickle cell disease (SCD) is a group of inherited disorders caused by a mutation of the hemoglobin gene, resulting in the formation of abnormal, sickle-shaped red blood cells. It is a lifelong condition characterized by anemia, vaso-occlusion, and decreased blood flow to vital tissues. Sickle cell disease affects every major organ and significantly reduces life expectancy of the affected individuals. Patients with SCD are at an increased risk for developing musculoskeletal complications that decrease quality of life and contribute to the significant burden of the disease. Understanding these complications, as well as the genetics, pathophysiology, and epidemiology of SCD, will assist orthopaedic nurses in providing evidence-informed care.