In recent years, close attention has been paid to the role of glycocalyx, a structural component of the vascular endothelium that is made up of glycoproteins, proteoglycans, sugar chains, etc. Glycocalyx has been shown to have diverse functions, including suppression of blood coagulation within the vascular lumen, as well as regulation of platelet/neutrophil adhesion to the vascular lumen, regulation of the vascular permeability, sensing of mechanical stimuli such as shear stress, etc. For technical and other reasons, few advances have been made in research on glycocalyx, which has quite delicate and fragile features. However, with the recent progress in testing methods, research on glycocalyx has entered a new phase. Now, glycocalyx is known to play important roles not only in the pathogenesis of acute diseases (e.g., sepsis and post-ischemic reperfusion disorders), but also in the pathogenesis of chronic diseases such as diabetes mellitus and atherosclerosis. In this paper, we present the latest findings on the structure and functions of glycocalyx and their relationships to illnesses, etc.