Phenotypic change of the smooth muscle cell (SMC) is implicated in normal development as well as several pathological processes including atherosclerosis. In general, differentiated SMCs show contractile responses to different exogenous stimuli and are inactive in mitosis, while undifferentiated or dedifferentiated SMCs show a mitogenic response and are not contractible. In the present review, we describe structural and functional aspects of the phenotypic change of SMCs with special reference to their role in atherogenesis. SMCs derived from atherosclerotic intimal lesions (intimal SMCs) show more amplified growth potential and chemotactic activity than medial SMCs; and, furthermore, they acquire a macrophage-like phenotype: uptake of modified low density lipoproteins through the scavenger receptor, which leads to high tendency toward foam cell formation. Platelet-derived growth factor, secreted from most of the cells existing in atherosclerotic plaques, is one of candidates that promote the formation of such a highly dedifferentiated intimal SMC. Clinical and experimental evidence supports the concept that an appearance of the pathological intimal SMCs is a key step for their abnormal proliferation in atheromatous lesions. Recent advances in characterization of the phenotype-specific molecular markers for SMC, such as myosin heavy chain, caldesmon, and calponin, are also described.