Can we prepare nanobiotechnology based blood substitutes with the following properties: sterilized to remove infective agents;used on the spot without typing and cross matching;store at room temperature for more than 1 year;unlimited supply.The HIV donor blood crisis in the late 1980s led people to become interested in the first report on nanobiotechnological red blood cell substitutes (Chang Science 1964).There was only time to develop simple oxygen carriers, like crosslinking of hemoglobin (Hb) into soluble complexes of PolyHb.(Later, also conjugated Hb,intramolecularly crosslinked Hb and recombinant Hb).PolyHb has been tested extensively in clinical trials including a recent one with about 700 hemorrhagic shock patients transfused in the ambulance before reaching the hospitals (Moore et al 2009).PolyHb has already been approved for routine use in South Africa and also Russia.In order to remove oXygen radicals to prevent ischemia-reperfusion injury, we have a soluble nanobiotechnological complex of PolyHb-CAT-SOD containing Hb, superoxide dismutase (SOD) and catalase (CAT).Since transport of intracellular carbon dioxide in severe hemorrhagic shock is important, we have a third generation system of PolyHb-CAT-SODCA (CA=carbonic anhydrase).We are also studying a 4th generation nanodimension complete artificial red blood cells…Platelet substitutes: massive bleeding requires supplements with platelets that are in very short supply with short storage time.We reported a soluble nanobiotechnological soluble PolyHb-fibrinogen complex.Unlike PolyHb,this can replace up to 98% of the blood volume in rats with no significant increase in clotting time.