At birth the transition by the fetal situation to neonatal life occurs. The real mechanism of lung liquid reabsorption and lung aereation at birth, in the past attributed only to the epithelial sodium channel function, has recently been linked to the first important breaths too and to the following changes in transpulmonary pressure. If this quite easily happens in the term baby, the preterm infants and all the babies with poor respiratory effort may have a delayed achievement of an adequate functional residual capacity (FRC). Premature delivery is always associated to the failure of respiratory transition and preterm babies frequently need a respiratory support (e.g., N-CPAP). Actual recommendations do not consider to mimic the physiologic changes that usually happen to the term neonate at birth. The application at birth of the sustained lung inflation (SLI) (a peak pressure of 25-30 cm H2O for 10-20 seconds), with nasopharyngeal tube or an adequately sized mask and a Neo-puff device, followed by the application of a continuous adequate PEEP (e.g., 5 cmH2O) is effective in the achievement of the FRC in animal studies and in the reduction of the need of mechanical ventilation (MV) in preterm infants at risk for RDS. Large RCTs are needed to verify the real efficacy of SLI in the delivery room to prevent the need of mechanical ventilation and to improve respiratory outcomes of preterm infants at risk for RDS.