Respiratory distress syndrome (RDS) is a syndrome caused by pulmonary insufficiency especially in premature infants. It is due to lack of alveolar surfactant along with structural immaturity of the lung. Although recent advances in the management of RDS, it is still a major cause of morbidity and mortality in premature infants. Surfactant replacement therapy is crucial in the management of RDS. Exogenous lung surfactant can be either natural or synthetic. Natural surfactant is extracted from animal sources such as bovine or porcine. Synthetic surfactant is manufactured from compounds that mimic natural surfactant properties. Until recently, natural surfactant extracts would seem to be the more desirable choice. Two basic strategies for surfactant replacement have emerged: prophylactic or preventive treatment, in which surfactant is administered at the time of birth or shortly thereafter to infants who are at high risk for developing RDS from surfactant deficiency; and rescue or therapeutic treatment, in which surfactant is administered after the initiation of mechanical ventilation in infants with clinically confirmed RDS. At least 100 mg/kg of phospholipid is required, but there are pharmacokinetic and clinical data suggesting that 200 mg/kg has a better clinical outcome. Recent recommended method is ‘INSURE’ (Intubate - SURfactant - Extubation) technique. After installation of pulmonary surfactant, reducing the high peak and fluctuations in oxygen saturation are important since these are associated with an increased incidence of retinopathy of prematurity. Non-invasive ventilatory support can reduce the adverse effects associated with intubation and mechanical ventilation, such as bronchopulmonary dysplasia.