Polymerized hemoglobin preparations have proven most successful in clinical trials due to their improved side-effect profile. The goal is to evaluate blood substitutes with enhanced intravascular retention, reduced osmotic activity, and attenuated hemodynamic derangements such as vasoconstriction. Although not without substantial morbidity and mortality, the current safety of allogeneic blood transfusion demands that comparative studies show minimal adverse effects, as well as efficacy and potential for novel applications.