Vascular smooth muscle cells accumulate excessively in the formation of neointima and have a key role in the pathogenesis of vasculoproliferative disorders such as atherosclerosis, allograft vasculopathy, bypass graft occlusion, in-stent restenosis and restenosis after percutaneous balloon angioplasty. To date there is no clinically established treatment to prevent the accumulation of smooth muscle cells in the neointima. However, much attention has been devoted to experimentally targeting the inhibition of migration and proliferation of medial smooth muscle cells. The recent identification of circulating bone marrow-derived smooth muscle progenitor has challenged the classical concept of infiltration of solely medial smooth muscle cells in the neointima. In addition, other potential sources such as circulating smooth muscle cell precursors that may not be of direct bone marrow origin, adventitial stem cells or smooth muscle cell progenitors that are released from other organs into the circulation have been demonstrated to have the potential to differentiate into smooth muscle cells. These discoveries have motivated us to reconsider how neointima forms in pathological conditions in the adult human. This update discusses recent insights on smooth muscle progenitors both from a biological and therapeutic perspective.