This chapter aims to demonstrate the perinatal respiratory distress syndrome in the newborn (RDS). Interventions to improve outcomes and prevent RDS should be started before birth. The best way to prevent it and its complications is adequate prenatal care in order to avoid premature labor. The diagnosis is based on the presence of significant respiratory distress in a premature newborn in the first hours after birth. The treatment of RDS includes the use of different methods of noninvasive or invasive ventilatory assistance; administration of exogenous surfactant; and general measures of thermal, metabolic, water, and hemodynamic control, when necessary. The important message is that the proper management of the disease from birth to discharge are fundamental for perinatal outcomes.