New blood vessels are formed through angiogenesis and postnatal vasculogenesis. Thus, it is essential to identify vascular stem and progenitor cell niches and the mechanisms governing their role in blood vessel formation. Although much is known about circulating and bone marrow-derived endothelial progenitor cells (EPCs), little is known about the vascular wall as an EPC niche. Experimental evidence strongly suggests that EPCs, as well as other stem and progenitor cells, reside in distinct zones of the vessel wall, such as within the subendothelial space and in the so-called “vasculogenic zone” within the vascular adventitia. In this review, we discuss the potential implications of different types of vascular wall resident stem and progenitor cells in health and disease.