Atherosclerosis (As) is a chronic disease involving several kinds of cells and induced by a variety of factors. The proliferation and migration of vascular smooth muscle cell (VSMC) have an important influence on the occurrence and development of As, including the promotion of the plaque formation and the instability of the plaque. Conversion of VSMC from contractile phenotype to synthetic phenotype is the basis of VSMC proliferation and migration. The maintanance of VSMC contractile phenotype is helpful to inhibit its abnormal proliferation and the plaque formation. Myocardin, as the key transcription factors of VSMC contraction marker genes, binds to serum response factor to facilitate expression of VSMC contraction marker genes. Many kinds of functional factors such as estrogen receptor α, histone modification, DNA methylation and microRNA, can be combined with myocardin, regulating vascular function and inhibiting the phenotype switch of VSMC; various channels, such as transforming growth factor-β1 and platelet derived growth factor-BB signaling pathway, can increase expression of myocardin to inhibit the proliferation and migration of VSMC. So myocardin plays an important role in the development of As. Regulating myocardin to affect the phenotype switch of VSMC may become a new therapeutic strategy for As and other cardiovascular diseases in the future.