Endothelial glycocalyx is a layer enriched with glycoproteins, proteoglycans and glycosaminoglycans covering the entire vascular surface of endotheliocytes. Some components of glycocalyx are exfoliated by the bloodstream and aggressive biological agents and simultaneously replenished with blood glycosaminoglycans. Dynamic equilibrium of endothelial glycocalyx structure is disturbed by accelerated exfoliation of its elements (shear-stress) following hypoxia, hyper- and hypovolemia, hyperglycemia, enzymatic and microbial invasion. Glycocalyx damage leads to further endothelial lesion and endotheliitis underlying multiple critical conditions. Prevention of endothelial glycocalyx damage and its potential remodulation are perspective for the treatment of critical conditions. However, such methods and drugs are still not studied enough. At the same time, various experimental and clinical studies have been published over the last 20—25 years. According to these data, various modern drugs ensure own therapeutic effect apparently affecting the structure and integrity of endothelial glycocalyx. Remodulation of damaged glycocalyx via infusion of albumin and fresh frozen plasma was experimentally observed. At the same time, infusion of colloidal solutions (dextran, hydroxyethyl starches) had no similar effect. The ability of glucocorticoids to stabilize and prevent glycocalix damage has been obtained in clinical studies in neonates undergoing surgical interventions. Long-term use of sulodexide contributed to a 2-fold decrease of proteinuria and thickening of glycocalyx in renal capillaries in patients with diabetes mellitus. This review also considers the possibilities of other drugs in prevention of glycocalyx damage and its remodulation.