Until recently, orthopedic surgery was strongly contraindicated in patients with hemophilia and inhibitors. However, recent advances in our knowledge of bypassing agents (particularly recombinant activated factor VII [rFVIIa]) that provide effective surgical hemostasis have allowed us to successfully perform major orthopedic procedures in these patients. Adequate hemostasis during surgery and postoperative rehabilitation is crucial, as development of a wound hematoma may jeopardize long-term outcomes. It also should be noted that success depends not only on appropriate drug therapy but also on preoperative preparations and adequate perioperative surveillance. Preoperative assessment of vascular status is very important, and strong motivation--on the part of the patient, the surgeon, and the hematologist--is needed to ensure a satisfactory result. Although inhibitor patients undergoing surgery face a higher risk of bleeding and other complications than their non-inhibitor counterparts, outcomes are generally good if a multidisciplinary team approach is applied.