Respiratory distress syndrome (RDS) impacts a high proportion of preterm neonates, resulting in significant morbidity and mortality. Advances in pharmacotherapy, specifically antenatal corticosteroids and postnatal surfactant therapy, have significantly reduced the incidence and impact of neonatal RDS. Antenatal corticosteroids accelerate fetal lung maturation by increasing the activity of enzymes responsible for surfactant biosynthesis, resulting in improved lung compliance. Maternal antenatal corticosteroid treatment has improved survival of preterm neonates and lowered the incidence of brain injury. After birth, exogenous surfactant administration improves lung compliance and oxygenation, resulting in reductions in the incidence of pneumothorax and of death. Future research will identify the optimal surfactant product, timing of the initial dose, and mode of delivery.