Surfactant replacement therapy for treatment or prevention of the respiratory distress syndrome (RDS) has been studied intensively over the past decade. Randomized controlled trials have demonstrated a reduction in the odds of neonatal death of about 40% and of pulmonary air leaks of 35 to 70% depending upon the type of surfactant used. Prophylaxis or very early treatment is superior to later treatment, especially for the very preterm (< 28 week) infant. Natural (derived from animal lungs) surfactants have a more rapid onset of action than synthetic surfactants and may also provide better long-term benefits, but further comparative trials will be needed to demonstrate this conclusively. Surfactant treatment should not be viewed as a substitute for prenatal steroid therapy to enhance fetal lung maturity; the treatments are synergistic.