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Approximately 10% of neonates require respiratory support immediately after delivery due to transitional problems or respiratory disorders, and up to 1% of neonates are in need of resuscitation. Respiratory distress is the most frequent cause of neonatal intensive care unit (NICU) admission, and the individual management strategies should be the main task in NICUs for these infants. Regardless of the cause, if not recognized and managed in advance, respiratory distress can escalate to respiratory failure and cardiopulmonary arrest. This chapter explores the evaluation and differential diagnosis of respiratory distress in neonates and presents an update on management strategies according to the protocol of Ankara University Children’s Hospital Neonatal Intensive Care Unit.