Significant physiological and pathophysiological processes involve interactions of specific lipoproteins with specific proteoglycans. So far, these interactions fall into two large groups. The first is interactions with heparan sulfate proteoglycans (HSPGs), primarily on the cell surface that lead to cellular uptake of the lipoproteins. These pathways are of interest because they involve endocytic machinery, intracellular itineraries, and regulation that are generally distinct from classic, coated pit-mediated endocytosis (1). Moreover, many important nonlipoprotein ligands, such as infectious agents, growth factors, platelet secretory products, and proteins implicated in Alzheimer’s disease, bind to the same HSPGs, and lipoproteins are a convenient model ligand to study HSPG-mediated catabolism. The second group of lipoprotein- proteoglycan interactions involves chondroitin sulfate proteoglycans (CSPGs), primarily in the extracellular matrix, leading to retention of cholesterol-rich lipoproteins. Many lines of evidence now support the concept that retention of lipoproteins within the arterial wall is the key initial step in provoking atherosclerosis, the major killer in Western countries (2,3t).