The endothelial glycocalyx (EG) is the most luminal layer of the blood vessel, growing on and within the vascular wall. Shedding of the EG plays a central role in many critical illnesses. Degradation of the EG is associated with increased morbidity and mortality. Certain illnesses and iatrogenic interventions can cause degradation of the EG. It is not known whether restitution of the EG promotes the survival of the patient. First trials that focus on the reorganization and/or restitution of the EG seem promising. Nevertheless, the step “from bench to bedside” is still a big one.