Stem/progenitor cells residing in the vascular wall of post-natal vessels play a crucial role in angiogenesis and vascular regeneration after damage. There are four major populations of vascular-resident stem/progenitor cells with differentiated clonogenic and proliferative potential, namely mesenchymal stem cells, pericytes, endothelial progenitor cells, and smooth muscle progenitor cells. These progenitors reside in vascular stem cell niches, which are more likely to be in the adventitia, a vascular wall layer in which increased concentration of stem cell surface markers has been shown. Indeed, vascular resident progenitors are not uniformly distributed across the vessel wall and the circulatory system. The heterogeneity of such a distribution could contribute to the differentiated susceptibility of various vessel regions to chronic vascular diseases such as atherosclerosis. In cardiovascular pathology, adult vascular resident progenitors could play either a negative or a positive role.