The major component of glycocalyx, heparan sulfate covalently attaches to proteoglycan core proteins, which is abundant at the cell surface and in the extracellular matrix. Heparan sulfate could provide binding sites on endothelial cells to retain and activate highly diffusible cytokines and inflammatory chemokines to regulate cell functions, such as proliferation and migration. Under physiological and pathological conditions, the remodeling in structure of heparan sulfate including the abnormal expression, and irregular distribution that critically play a fundamental role in inflammation and atherosclerosis, as well as many other diseases was observed. This book aims to integrate a current understanding of the identified molecular mechanisms in the regulation of glycocalyx, especially the heparan sulfate structure. Additionally, the available drugs that can protect the heparan sulfate or induce its synthesis, and the measurement techniques of the endothelial glycocalyx, as well as the relationship between structure and function of heparan sulfate in the progression of inflammation and atherosclerosis are analyzed.