Unraveling the contribution of stem and progenitor cells to blood vessel formation and, reciprocally, the importance of blood vessels to the production and function of stem and progenitor cells, has been a major focus of vascular research over the last decade, but has spawned many controversies. Here I review how vascular stem and progenitor cells contribute both vascular and nonvascular cells during development and in disease, and how nonvascular stem and progenitor cells might contribute to vascular lineages. I also discuss the role of the vasculature in forming stem and progenitor cell niches. Finally, I highlight the potential relevance of these relationships to disease etiology and treatment.