Allogeneic blood transfusion increase infectious complications, morbidity, mortality, and length of stay in hospitalized patients, and the risk is directly proportional to the number of blood transfusions. Apart from direct transmission of various infectious organisms, allogeneic blood transfusions also introduce a multitude of foreign antigens, which lead to either immune activation (transfusion-associated graft-vs-host disease, transfusion-related lung injury, alloimmunization and various autoimmune diseases) or tolerance induction (predisposition to nosocomial and postoperative infections, cancer recurrence, microchimerism and enhanced survival of allograft). Thus there is a need for artificial oxygen carriers which can be used as alternatives to allogeneic blood transfusions to improve tissue oxygenation and function of organs with marginal oxygen supply. But the search for alternative strategies to carry oxygen to the tissues has eluded investigators for centuries. Another important reason for the need of blood substitutes is the non-availability of allogeneic blood in the setting of traumatic hemorrhage because of the paucity of universal donor-type blood, the length of time required for type and cross-matching, and the limited blood bank inventory secondary to the short shelf life of red blood cells. Hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon emulsions seem promising artificial oxygen carriers and may occupy a more prominent position in the near future.