Human alloantibodies to factor VIII occur in 15-50% of patients with severe hemophilia A. The development of these inhibitory alloantibodies prevents treatment with replacement factor VIII and places the patient at higher risk for complications from bleeding. Immune tolerance to factor VIII can be achieved in patients with inhibitors through the regular administration of factor VIII. The mechanism by which immune tolerance is achieved is unclear but the regular administration of factor VIII is believed to interrupt the normal immune mechanisms, perhaps by altering antigen presentation and inducing T or B cell anergy. The development of immune tolerance in hemophilia can be seen as a potential model for the development of methods for inducing tolerance to other alloimmune and autoimmune disorders.