Pulmonary vascular disease embodies all congenital or acquired pathologies that affect the pulmonary vasculature. One of them is pulmonary hypertension of the newborn (PHN), which is clinically characterized by a persistent high pulmonary vascular resistance postnatally and an abnormal vascular response. Morphologically, the vascular walls of the small pulmonary arteries become thickened, leading to increased resistance of these vessels and thus a worsening of gas exchange. PHN occurs as a primary disease or in association with abnormal lung development, for example as in congenital diaphragmatic hernia, and is a critical determinant of morbidity and mortality. Here we review the current knowledge about vascular abnormalities in PHN and discuss the vascular abnormalities in different conditions associated with pulmonary hypertension in human newborns in relation to recent findings from molecular biology.