Healthy vascular endothelium is luminally coated by an endothelial glycocalyx, which interacts with the bloodstream and assumes a filter function on the vascular wall. Although this structure was discovered nearly 70 years ago, its physiological importance has been underestimated for a long time. Recent findings indicate that the glycocalyx is, in addition to the endothelial cells themselves, a main constituent part of the vascular barrier. The existence of different colloid osmotic gradients within and beneath this structure has now led to a modification of the Starling equation. In many vascular beds the interstitial space features a protein concentration similar to that of the plasma. The inwardly directed gradient, which retains water and proteins in the vascular system, is generated beneath the glycocalyx by selective protein filtration over this structure. The endothelial glycocalyx, as an additional competent vascular permeability barrier has, therefore, not only a key role for perioperative fluid and protein shifts into the interstitial space, but it seems to be intimately involved in the pathophysiology of diabetes, arteriosclerosis, sepsis and ischemia/reperfusion, especially with respect to associated vascular dysfunctions. The fragile glycocalyx can be destroyed in the course of surgery, trauma, ischemia/reperfusion and sepsis and by inflammatory mediators such as TNF-alpha, causing leukocyte adhesion, platelet aggregation and edema formation. Recent studies have shown that protecting this structure not only maintains the vascular barrier, but constitutes an important component of a rational perioperative fluid therapy.