The transition from the intrauterine environment to the extrauterine environment is one of the most dramatic physiologic changes that a human experiences. Over the course of a few breaths, the lung changes from a primarily secretory organ to a primarily absorptive organ, the epithelium transitions from a liquid–liquid interface to an air–liquid interface, and responsibility for gas exchange shifts from the placenta to the lungs, which now receive significantly more blood flow. The normal neonatal lung demonstrates bronchovascular bundles containing the airways and the pulmonary arteries, complex alveoli comprised primarily of flat type I alveolar epithelial cells interspersed with plump type II alveolar epithelial cells, and an interstitium comprised primarily of capillaries for rapid gas exchange and pulmonary veins. Somehow all these processes progress normally in every delivered healthy baby. The infant faces a series of physiologic challenges through the neonatal period as the infant adjusts to the transition from the intrauterine environment to the extrauterine environment. For example, while the very compliant chest wall eases passage through the birth canal, it impairs pulmonary mechanics in the postnatal period. In this chapter, we discuss these normal processes as well as the means by which things go wrong, including transient tachypnea of the newborn, persistent pulmonary hypertension of the newborn, bronchopulmonary dysplasia, and defects of lung development including congenital diaphragmatic hernia. We focus on the key areas of mechanics, pulmonary blood flow, and respiratory control to highlight the physiologic changes that occur in the neonate.