Respiratory distress syndrome, formerly known by the name of hyaline membrane disease is a syndrome characterised by the interaction of structural immaturity of the lungs and the lack of surfactant, which is most commonly the consequence of prematurity. Clinical manifestations occur within the very first minutes after labour and include tachypnea, activation of accessory respiratory muscles, widening of nose wings, head nodding, inspiratory retractions of intercostal spaces, sternum and xiphoid, with simultaneous protrusion of the abdominal wall and further progression leading to cyanosis. The diagnosis is confirmed by laboratory blood tests and specific radiographic changes on the chest x-ray. Prevention refers to prompt recognition of the signs indicative of potential premature labour within a timeframe between 1 and 7 days, and antenatal application of corticosteroids between 23rd and 34th week of gestation with the purpose of pneumocytes type 2 maturation induction and surfactant production. However, if preamature labour does indeed occur and antenatal corticosteroids have not been timely applied in premature newborns with the risk of developing RDS, or already developed RDS without respiratory failure, the application of nCPAP as a non-invasive method of ventilation has initial advantage in comparison to endotracheal intubation, exogenous application of surfactant and mechanical ventilation. With worsening of the condition, the needs of greater inspiratory oxygen fraction and the onset of respiratory acidosis or severe apnoea, an indication for mechanical ventilation and exogenous surfactant application arises. Aside from the RDS, some other potential causes of respiratory distress should be excluded such as TTN, bacterial pneumonia, pneumothorax, PPHN, meconium aspiration syndrome and congenital heart defects, since their symptoms might resemble to those of the RDS.