Blood vessels serve as the conduit by which O2 and nutrients are delivered to body tissues. In patients with atherosclerotic cardiovascular disease, arterial stenosis results in decreased tissue perfusion and ischemia. Decreased O2 levels in ischemic tissue lead to increased activity of hypoxia-inducible factor 1 (HIF-1), which mediates transcription of genes encoding angiogenic growth factors such as vascular endothelial growth factor and stromal-derived factor 1. These angiogenic factors activate endothelial cells in the ischemic tissue and induce the mobilization into peripheral blood of CD34+/VEGFR2+ and CXCR4+/Sca1+ circulating angiogenic cells (CACs), which home to the ischemic tissue, where they promote angiogenesis and arteriogenesis. Aging impairs the physiological response pathway through which hypoxia induces HIF-1 activity, angiogenic growth factor expression, CAC mobilization, and tissue vascularization. In a mouse model of limb ischemia, HIF-1 gene therapy was sufficient to overcome the aging-associated impairment of ischemia-induced vascularization (1). Tumor growth is dependent on the formation of blood vessels. A novel strategy for treating cancer is metronomic therapy, which involves the administration of lower doses of chemotherapy at more frequent intervals. Metronomic administration of several chemotherapeutic agents has been shown to block blood vessel formation, thereby inhibiting tumor growth. However, the mechanism by which metronomic chemotherapy inhibits tumor vascularization has not been determined. For one class of commonly-used chemotherapeutic agents, we have found that daily administration inhibits HIF-1 transcriptional activity, leading to decreased expression of angiogenic growth factors in tumor xenografts and peripheral blood, decreased mobilization of CD34+/VEGFR2+, CXCR4+/Sca1+, and CD117+/VEGFR2+ CACs into peripheral blood, decreased tumor vascularization, and a dramatic arrest of tumor growth (2).