Sickle cell disease is an inherited hemoglobinopathy that develops from a genetic mutation and the production of a dysfunctional variant of hemoglobin. A number of physiological disturbances encountered during the perioperative period (blood loss, hypotension, acidosis, and hypoxia) may induce "sickling" of the biochemically altered hemoglobin, producing painful microvascular occlusion, hemolytic anemia, and impaired oxygen delivery. The only available curative therapy requires bone marrow transplantation. The purpose of this article is to review the pathophysiology of sickle cell disease and the pertinent preoperative, intraoperative, and postoperative care of patients with the disease.