At least three distinct cellular mechanisms are currently thought to be responsible for the initiation of atherosclerotic lesions in humans: (1) accumulation of lipids and plasma-derived lipoproteins in the arterial intima; (2) smooth muscle cell migration from the media into the intima, and smooth muscle cell proliferation or accumulation, or both, within the intima; and (3) accumulation of platelet and/or fibrin deposits in the intima. Independent of the triggering factor, it appears that the first step in atherogenesis involves activation of repair mechanisms in the blood vessel in an attempt to restore vascular homeostasis, which involves a delicate balance of growth promoting and growth inhibitory activities of the vascular wall cells. The healing process involves a series of specific and temporally coordinated events, such as platelet aggregation, monocyte adhesion and migration across endothelial cells, and migration and proliferation of vascular smooth muscle cells, which are normally orchestrated by a variety of growth factors, cytokines, adhesion molecules, and extracellular matrix proteins in a controlled, although not yet fully understood, manner. Alteration in any of these steps during the healing process can lead to changes in the patterns of protein synthesis, processing, and secretion in these cells. These in turn result in connective tissue deposition, lipid accumulation, cell death, mineralization, and finally the development of advanced, occluding atherosclerotic plaques.