The use of mechanical ventilation in premature infants with respiratory distress syndrome (RDS) and respiratory failure often results in barotrauma, volutrauma and chronic lung disease (CLD). Research indicates that early surfactant therapy and initiation of nasal continuous positive airway pressure (CPAP) for these infants significantly reduces the need for mechanical ventilation and the incidence of CLD. Different CPAP delivery systems exist, each with some practical and clinical advantages and disadvantages. Clinical trials indicate that optimal management of neonatal RDS could be improved by early surfactant treatment followed immediately by extubation and stabilization on CPAP. Evidence suggests a synergistic effect between early surfactant administration (within 2 h of birth) and rapid extubation to nasal CPAP with a significant reduction in the need for mechanical ventilation and its associated morbidities.