The in utero environment of the pulmonary circulation is unique. During fetal life, the lung is fluid filled, oxygen tension low, pulmonary blood flow limited, and pulmonary vascular resistance exceeds systemic vascular resistance. Blood is shunted away from the lungs at the level of the ductus arteriosus. At birth, pulmonary blood flow increases eightfold to tenfold and pulmonary artery pressure decreases to 50% of systemic levels within 24 h after birth concomitant with an increase in oxygen tension. The critical physiologic stimuli that account for perinatal pulmonary vasodilation include rhythmic distention of the lung and an increase in both shear stress and oxygen tension. Data accumulated over the past several decades implicate distinct and complementary roles for both pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth cells (PASMCs) in promoting fetal lung growth and development and in mediating the postnatal adaptation of the pulmonary circulation.