BACKGROUND The inherent risks of blood transfusion have led to concerted efforts to find alternatives to allogeneic blood transfusion. Among these alternatives are supplementation with iron and treatment with erythropoietin, autologous pre-donation before major elective surgery, intraoperative blood salvage (particularly for emergency cases or when major blood loss is unanticipated), acute normovolemic hemodilution, and artificial blood substitutes. METHODS Review of pertinent English-language literature. RESULTS Autologous pre-donation of the patient's own blood, even if supplemented with iron and erythropoietin, is increasingly out of favor for several reasons. Autologous pre-donation is an added out-of-pocket expense for the patient. The major cause of incompatible blood transfusion, namely clerical error, is not eliminated. Moreover, autologous pre-donated blood is not released to the general blood supply; therefore, autologous blood that is not returned to the patient by infusion is wasted. Acute normovolemic hemodilution is a safe alternative that eliminates the risk of mistransfusion, minimizes the shed red cell mass when bleeding occurs, and reduces the risk of perioperative transfusion as shown in patients undergoing radical prostatectomy. CONCLUSIONS Acute normovolemic hemodilution achieves equivalent outcomes at lower cost compared with autologous pre-donation. Patient safety is increased, and if pharmacologic strategies are combined with acute normovolemic hemodilution, allogeneic blood transfusion may be eliminated entirely.