Studies of bone morphogenesis have identified a large number of critical molecules and regulatory pathways. One of these molecules is vascular endothelial growth factor, VEGF. Several studies suggest that not only is this regulator of angiogenesis important in mediating interactions between the developing bone and the vasculature, but it also has a key role in regulating processes during bone development and growth which are not directly related to angiogenesis. Studies of the detailed mechanisms by which VEGF is involved in bone development promise therefore to shed new light on key steps in bone formation. This chapter summarizes findings with emphasis on the developmental roles of VEGF in skeletal morphogenesis. Furthermore, we speculate on the future directions of research in this area and describe some of the challenges in the field.