The circulation is adapted to specific levels of blood viscosity resulting in a balance that simultaneously sets peripheral vascular resistance, blood pressure and cardiac output, factors in part mediated by the production of nitric oxide by the endothelium. Although it is generally perceived that decreasing blood viscosity is beneficial for cardiovascular function, small increases of blood viscosity in normal healthy experimental subjects significantly improve cardiovascular function. These changes are within the normal variations of viscosity due to the variations of hematocrit in the healthy population. Hemodilution reduces blood viscosity, which is proposed to be physiologically beneficial. However, in extreme hemodilution, increased plasma viscosity via the use of viscogenic plasma expanders sustains microvascular and tissue function at significantly reduced levels of oxygen delivery. Studies in hemorrhagic shock resuscitation using oxygen carrying and non-carrying red blood cells show that restoration of blood viscosity is as important as restoration of oxygen carrying capacity. It is concluded that although hemodilution is indicated for reducing abnormally high blood viscosities, it is beneficial to increase plasma viscosity when hematocrit is reduced. Furthermore small increases in hematocrit may be beneficial due to the related increase in blood viscosity, independently of the increase of oxygen delivery capacity.