The respiratory distress is a very common condition both in term and in preterm neonates and the most frequent reason for admission to the neonatal intensive care unit (NICU). The aetiology greatly depends on the maturation of neonate's organs and perinatal events. The clinical picture is sometimes scarce and very nonspecific for the etiologic determination. Treatment of neonatal RD begins first with the application of a mixture of oxygen and air, then with different modes of non-invasive respiratory support methods. Non-invasive respiratory support can be sustained with nasal continuous positive airway pressure, bi-level positive airway pressure and high-flow nasal cannula ventilation. Non-invasive ventilation with high-frequency oscillations through nasal cannula or masks is also possible with some respiratory devices. Non-invasive ventilation is usually combined with the application of natural surfactant and other therapeutic means, like methylxanthine therapy, prevention and closure of patent ductus arteriosus, and control of infection. In the case of non-invasive ventilation failure, different kinds of invasive ventilation methods are available and being practiced in NICUs. The invasive respiratory support can be maintained by controlled or intermittent mandatory ventilation combined with different supportive synchronous positive inspiratory ventilation, offered by modern respirators.