OBJECTIVE More than 8.5 million people in the world observe the Jehovah's Witness faith, and require unique consideration for perioperative blood management as they generally refuse transfusion of blood and blood products. This review addresses a collaborative approach to each patient throughout the perioperative arena. The principles of this approach include optimization of hemoglobin levels preoperatively, attention to blood-salvaging methods intraoperatively, and minimization of blood draws postoperatively. In addition, we review the technologies currently in development as transfusion alternatives, including hemoglobin-based oxygen carriers. RESULTS Progress has been made recently in the field of synthetic blood alternatives and hemoglobin-based oxygen carriers, which may lead to improved outcomes in this patient population. CONCLUSIONS Utilization of multiple prevention and mitigation strategies to optimize oxygen supply and decrease oxygen demand will lead to decreased incidence of critical anemia and subsequent improved mortality in Jehovah's Witness patients.