Treatment of severe hemorrhage offers few theoretical problems, but in practice, severe blood loss usually occurs out of hospital, often in more or less inaccessible scenarios. Controversy rages over ideal fluid, ideal volume, and minimum O2 carrying capacity, but all agree that pre-hospital, isotonic resuscitation is unfeasible. The effects of highly hypertonic 7.5% NaCl (HS) was first described in 1980, when we showed that it induced immediate and long lasting hemodynamic restoration. The addition of 6% dextran-70 to (HSD) significantly enhances the duration and intensity of volume expansion, with no loss of hemodynamic effects. HS/HSD restores cardiac output, arterial pressure, base excess and oxygen availability, induce pre-capillary vasodialtion, moderate hyperosmolarity and hypernatremia, reversal of high glucose and lactate. It interferes with endocrine secretions when administered to animals in hemorrhagic hypotension. HS acts through transient plasma volume expansion, positive inotropic effect on cardiac contractility, precapillary vasodilation through a direct action on vascular smooth muscle. Expansion of circulating volume is part of the mechanism, the extra volume coming from the intracellular compartment fluid, especially from endothelial and red blood cells, which facilitate microcirculatory flow. The new field of interactions of hypertonicity with the immune mechanisms may provide insight into the long lasting effects of hypertonic solutions. Randomized double blind prospective studies on the effects of HS, or HSD, used as first treatment of shock show that both are safe and free from collateral, toxic effects. These studies show an early significant rise in arterial blood pressure and a non-significant trend towards higher levels of survival. HSD administration to patients about to undergo cardiopulmonary bypass for cardiac surgery results in higher cardiac output before, and immediately following cardiopulmonary bypass, as well as zero fluid balance.