Factor VIII (FVIII) replacement therapy is the foundation of treatment in hemophilia A and is effective unless a patient develops an alloantibody (inhibitor) against exogenous FVIII. Inhibitor development is currently the most significant treatment complication seen in patients with hemophilia and is associated with considerable morbidity and a decreased quality of life. The development of an inhibitor is the result of a complex interaction between a patient’s immune system and genetic and environmental risk factors. The mainstay of treatment is the eradication of the inhibitor through immune tolerance. This review summarizes the current evidence regarding inhibitor risk factors, eradication, and hemostatic bypassing agents.