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Lungs of preterm infants are deficient in surfactant, resulting in poor compliance. Surfactant replacement therapy is a standard therapy in infants with severe surfactant insufficiency. Surfactant preparations available in the market include natural (bovine, porcine) and synthetic varieties. There is debate over the choice of surfactant, timing, and threshold for surfactant therapy. Prophylactic or early rescue strategy has been shown to result in better outcomes than delayed administration. Recent data suggest that newer synthetic surfactants are as efficacious as natural varieties. Of late, innovative non-invasive methods of surfactant administration have obviated the need for intubation.