Abstract Of diverse growth factors that contribute to normal lung development, vascular endothelial growth factor (VEGF) plays an especially prominent role in the normal growth and development of the pulmonary circulation in the fetus and newborn. Strong experimental and clinical data support the role of impaired VEGF signaling in the pathogenesis of two major clinical disorders of the developing lung circulation: persistent pulmonary hypertension of the newborn (PPHN) and bronchopulmonary dysplasia (BPD). These disorders are each characterized by impaired vascular growth, structure and reactivity, which are at least partly due to endothelial cell dysfunction. This chapter will briefly discuss VEGF signaling during normal lung development and how disruption of VEGF signaling contribute to the pathogenesis of neonatal pulmonary vascular disease in these settings.