Transfusion therapy is frequently used in the treatment of sickle cell disease and its complications, but its efficacy has not been well proven. Red cell transfusions are well established for the acute treatment of cerebrovascular accidents and for the prevention of their recurrence. Acute chest syndrome with respiratory insufficiency is also an established indication for transfusion, especially in children. The use of red cell transfusions, especially chronic transfusions, in the treatment of sickle cell disease should be initiated only after serious consideration of the clinical setting and possible adverse effects. Both risks and benefits should be discussed with the patient, and that discussion should be documented.