The existence of a causal relation between elevated cholesterol levels and atherosclerosis is now considered an established fact, while cellular and molecular mechanisms underlying this relationship begin only now to be unravelled. The first stage of atherosclerosis development is the fatty streak, a focal accumulation of blood-derived lipid-laden macrophages in the arterial intima. The endothelium, which plays a pivotal role in vascular homeostasis, undergoes major functional changes under the influence of "oxidized" and "minimally-modified"-LDL, able to promote "endothelial activation", with the expression of adhesion molecules and chemoattractants for monocytes. Endothelial activation seems to be the transducer of atherogenic signals in the first stages of development of atherosclerosis. LDL also play a further crucial role in the progression and the instabilization of the plaque, and in the pathogenesis of functional changes of vasomotor tone.