Blood vessel formation plays a key role in both physiologic and pathologic tissue growth and healing. Thus, a thorough understanding of the mechanisms underlying neovascularization will translate into innovative clinical treatment strategies for a wide variety of disease processes. Vascular precursor/progenitor cell populations have been isolated from several different tissue types and have a rich potential for use in vascular regenerative strategies. Furthermore, levels of circulating endothelial progenitor cells (EPC) have been shown to correlate with outcomes in cardiovascular and vascular diseases. Treatment with EPC has been shown to improve functional outcomes following cardiac and peripheral vascular ischemia. Recent studies have also demonstrated a role for EPC in pediatric disease processes such as retinopathy of prematurity and bronchopulmonary dysplasia. In addition, many of the drugs utilized to treat vascular disease impact EPC mobilization and function. Importantly, the type of vascular injury appears to dictate the mechanism of neovascularization, highlighting the importance of carefully selected vascular regenerative strategies.