Human placental development involves co-ordinated angiogenesis and trophoblast outgrowth that are compromised in intrauterine growth restriction. Adaptive angiogenesis in IUGR placental villi is a result of an imbalance in the orderly progression of the expression profile of vascular endothelial growth factor, placenta growth factor and angiopoietin during placental development. VEGF receptors and the angiopoietin receptor Tie-2 are expressed on trophoblast, and their activation leads to trophoblast proliferation, migration and production of nitric oxide. Thus, these vascular factors act as autocrine regulators of trophoblast behaviour in the development of the utero-/feto-placental circulation, an action independent of their well-established roles in vascular endothelium.