Heparan sulfate glycosaminoglycans (HSGAGs) are an important subset of complex polysaccharides that represent the third major class of biopolymer, along with polynucleic acids and polypeptides. However, the importance of HSGAGs in biological processes is underappreciated because of a lack of effective molecular tools to correlate specific structures with functions. Only recently have significant strides been made in understanding the steps of HSGAG biosynthesis that lead to the formation of unique structures of functional importance. Such advances now create possibilities for intervening in numerous clinical situations, creating much-needed novel therapies for a variety of pathophysiological conditions including atherosclerosis, thromboembolic disorders, and unstable angina.