The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis has been that their 'aberrant' proliferation promotes plaque formation, while VSMCs in advanced plaques are beneficial for preventing rupture of the fibrous cap. However, recent studies using genetic lineage tracing have shown that VSMC phenotypic switching results in less differentiated forms, including macrophage-like cells, which directly promote atherosclerosis. VSMC proliferation may be beneficial throughout atherogenesis, and VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. The embryological origin of VSMCs influences their behavior in atherosclerosis, and the role of individual processes such as phenotypic switching, proliferation, migration, cell death, and senescence varies at different stages and regions of the plaque. The complexity of these processes reflects the intricate cellular and extracellular environment of atherosclerotic plaques. Understanding the biology of each major cell type contributing to late-stage lesion development is crucial for developing novel therapeutic approaches to treat atherosclerosis and reduce major clinical consequences.The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis has been that their 'aberrant' proliferation promotes plaque formation, while VSMCs in advanced plaques are beneficial for preventing rupture of the fibrous cap. However, recent studies using genetic lineage tracing have shown that VSMC phenotypic switching results in less differentiated forms, including macrophage-like cells, which directly promote atherosclerosis. VSMC proliferation may be beneficial throughout atherogenesis, and VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. The embryological origin of VSMCs influences their behavior in atherosclerosis, and the role of individual processes such as phenotypic switching, proliferation, migration, cell death, and senescence varies at different stages and regions of the plaque. The complexity of these processes reflects the intricate cellular and extracellular environment of atherosclerotic plaques. Understanding the biology of each major cell type contributing to late-stage lesion development is crucial for developing novel therapeutic approaches to treat atherosclerosis and reduce major clinical consequences.