Newborn respiratory distress is one of the most common reasons for neonatal intensive care admission at birth. If not diagnosed and managed appropriately, newborn respiratory distress can progress to cardiopulmonary collapse and death. Presenting symptoms of respiratory distress consist of increased work of breathing (eg, grunting, nasal flaring, cyanosis, retractions, respiratory rate greater than 60 breaths/min [tachypnea]). The most common cause of respiratory distress at term is transient tachypnea of the newborn. Other causes include respiratory distress syndrome, meconium aspiration syndrome, pneumonia, and sepsis. Less common causes are pneumothorax, congenital heart disease, and congenital diaphragmatic hernia. Physicians attending deliveries should be familiar with current neonatal resuscitation guidelines. If respiratory distress does not resolve after stabilization in the delivery room, chest radiography, supplemental oxygen, and appropriate laboratory tests (eg, complete blood cell count, blood cultures, C-reactive protein, blood gas measurement) should be considered. The Early-Onset Sepsis Calculator can help guide decision-making for neonates who may require antibiotic therapy.