Vascular smooth muscle cells have been the subject of intense study because of their importance in vascular disease process. Although significant progress has been made toward defining the various growth factors affecting the smooth muscle phenotype, very little is known about factors that promote smooth muscle differentiation. In the past few years, a number of key advances have been made in our understanding of skeletal muscle myogenesis, with the discovery of myogenic determination genes. In spite of these advances, the development and differentiation of smooth muscle cells remain vastly underexplored. This review is an attempt to understand the current status of the field and to highlight some of the recent progress made toward this goal.