The endothelium is a highly dynamic cell layer that is involved in a multitude of physiological functions, including the control of vascular tone, the movement of cells and nutrients, the maintenance of blood fluidity and the growth of new vessels. During severe sepsis, the endothelium becomes proadhesive, procoagulant, antifibrinolytic and is characterized by alterations of vasomotor regulation. Most of these functions have been discovered using in vitro and animal models, but in vivo exploration of endothelium in patients remains difficult. New tools to analyze endothelial dysfunction at bedside have to be developed.