The approach to minimizing transfusion therapy in the cardiac surgical patient entails an understanding of the unique physiology of CPB. A comprehensive blood conservation program will promote autologous reinfusion techniques and pharmacologic agents that preserve hemostasis. The institution of therapy-directed algorithms using appropriately selected tests will ultimately reduce empiric transfusions and will improve specificity of transfusion therapy. The use of technologies and drugs that attenuate inflammation will reduce consumption and the activation of leukocytes and platelets. This approach should be a multifaceted one that will ultimately lead to better preservation of end-organ function after cardiac surgery.