This obvious and simple statement of biological fact does not do justice to the physiological and pharmacological implications of the relationship. The vasculature is, of course, the conduit for calcium phosphate and nutrient exchange between bone and the rest of the body; this is relevant not only to the rapid mobilization of skeletal calcium when urgently needed (4) but also to the delivery of metabolic substrate to the basic multicellular unit (BMU) for bone-forming osteoblast functions. (5) However, the vasculature also provides the sustentacular niche for osteoblast progenitors, (6) and is the conduit for egress of bone marrow-derived formed elements from the osteoblast-regulated hematopoietic niche. (7) Indeed, Ignarro and colleagues (8) have coupled parathyroid hormone (PTH)-mediated bone anabolism with granulocyte colony stimulating factor (G-CSF) treatment as a strategy to mobilize endothelial progenitor cells (ePCs) and enhance ischemic limb recovery in mice. Surprisingly, the inextricable interdependence of vascular physiology, skeletogenesis, bone remodeling, and mineral metabolism has escaped widespread appreciation until very recently. Studies by Clemens et al. (9) established that the constitutive elaboration of vascular endothelial growth factor A (VEGF) by osteoblasts increases bone formation via mechanisms that require expansion of skeletal vascularity. They went on to show that pharmacologic augmentation of endogenous skeletal VEGF production accelerates skeletal repair during distraction osteogenesis. (10) Exogenous VEGF implants exhibit similar properties in critical bone defects. (11) However, the regulation of bone vascular biology and anatomy in response to metabolic, morphogenetic, mechanical, inflammatory, and endocrine cues is very poorly understood. A fundamental understanding of bone-vascular interactions will be necessary to develop new strategies that safely and efficaciously enhance bone formation in the settings of malignancy, fracture nonunion, the open epiphyses of childhood, and the arteriosclerotic vasculopathy of diabetes, uremia, rheumatoid arthritis, and advanced age.