The normal microvascular perfusion pattern is characterized by temporal and spatial variations of capillary flow. Local driving pressure, arteriolar vasomotion and endothelial cells are key-factors for local regulation of hydraulic resistance and fluid balance between the blood and tissue compartments. In shock, both the central and particularly the local mechanisms controlling microvascular perfusion are impaired. The microvascular perfusion pattern becomes permanently inhomogeneous due to lack of arteriolar vasomotion, changes of flow properties of blood, endothelial cell swelling and blood cell-endothelium interaction. Hence the objectives of primary shock therapy are to reestablish precapillary pressure, arteriolar vasomotion and to open the occluded microvascular pathways in order to reestablish the surface area needed for exchange of nutrients and drainage of waste product. These effects can not be achieved by vasoactive drugs, unless blood volume has been restored and blood fluidity improved by hemodilution. Whereas the necessary hemodilution can be achieved by conventional volume substitutes (colloids, crystalloids) restoration of vasomotion and reopening of narrowed capillaries can be obtained by small volume resuscitation using hyperosmotic/hyperoncotic salt dextran solution. The potential of this new concept for primary resuscitation and treatment of tissue ischemia is presently explored.