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In recent years, much progress has been made in elucidating the complex but orchestrated series of molecular events that drives a vascular smooth muscle cell to undergo proliferation. These events are initiated by mitogenic stimuli, such as platelet-derived growth factor binding to its receptor and triggering an intracellular signal transduction cascade, leading ultimately to cell-cycle progression and cell division. The signaling pathways that take place in response to both hyperplastic and hypertrophic agents, which include the mitogen-activated protein kinase and p70 S6 kinase, are discussed. In addition, novel protein kinase mediators, such as phosphatidylinositol 3-kinase and protein kinase B, and mechanisms that have recently been implicated in vascular smooth muscle cell growth are described.