Acute respiratory failure is the most common problem seen in the preterm and term infants admitted to neonatal intensive care units. In preterm infants, the most common cause of acute respiratory failure is respiratory distress syndrome caused by surfactant deficiency. Acute respiratory failure in term and near term infants is usually a result of meconium aspiration syndrome, sepsis, pulmonary hypoplasia, and primary pulmonary hypertension of the newborn. The response to various methods of treatment may vary, depending on the severity of respiratory failure and the cause of the acute respiratory failure. We reviewed the evidence for efficacy and current utilization of newer treatment modalities, including exogenous surfactant administration, high frequency ventilation, inhaled nitric oxide therapy, antenatal steroids for the prevention of respiratory distress syndrome, and use of postnatal steroids for the prevention of chronic lung disease.