The endothelial cell and subendothelial cell matrix provide a stage for several interactions that mediate lipoprotein transport, retention, and modification during atherogenesis. Many novel mechanisms in these processes have been uncovered. The endothelium regulates circulating plasma lipoproteins by acting as the site of action of the triglyceride hydrolyzing enzyme, lipoprotein lipase. Endothelial cells synthesize proteoglycans that anchor this enzyme, affect the actions of growth factors, and directly interact with some classes of lipoproteins. Recent studies have provided insights into the initiation of monocyte entry and the regulation of macrophage lipid uptake. Endothelial cell adhesion molecules are required for the recruitment of monocytes and, therefore, are essential to the atherosclerotic process. Understanding cellular and molecular pathways underlying the early stages of atherosclerosis may provide a rational basis for therapeutic intervention of this disease.