The presence of ectopic tissue in the diseased artery wall is evidence for the presence of multipotential stem cells in the vasculature. Mesenchymal stem cells were first identified in the marrow stroma, and they differentiate along multiple lineages giving rise to cartilage, bone, fat, muscle, and vascular tissue in vitro and in vivo. Transplantation studies show that marrow-derived mesenchymal stem cells appear to enter the circulation and engraft other tissues, including the artery wall, at sites of injury. Recent evidence indicates that mesenchymal stem cells are also present in normal artery wall and microvessels and that they also may enter the circulation, contributing to the population of circulating progenitor cells and engrafting other tissues. Thus, the artery wall is not only a destination but also a source of progenitor cells that have regenerative potential. Although potential artifacts, such as fusion, need to be taken into consideration, these new developments in vascular biology open important therapeutic avenues. A greater understanding of how mesenchymal stem cells from the bone marrow or artery wall bring about vascular regeneration and repair may lead to novel cell-based treatments for cardiovascular disease.