This review provides an update on recent advances in the field of molecular mechanisms of vascular bed development. We introduce the data about growth factors and their receptors and discuss the therapeutic potential of their modulation. The role of tissue hypoxia in vessel development is presented and documented by our own results. We review the role of ephrins and their receptors in differentiation of arterial and venous phenotype of endothelial cells and its loss in vein graft during adaptation to arterial circulation. Role of mutation in Foxc2 associated with valve failure in veins is discussed. Recent findings showing common genetic signals navigating blood vessels and nerves to common pathways are also described. Finally, we summarize current state of knowledge in therapeutic induction and inhibition of angiogenesis.