Newborn respiratory distress presents a diagnostic and management challenge. Newborns with respiratory distress commonly exhibit tachypnea with a respiratory rate of more than 60 respirations per minute. They may present with grunting, retractions, nasal flaring, and cyanosis. Common causes include transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, pneumonia, sepsis, pneumothorax, persistent pulmonary hypertension of the newborn, and delayed transition. Congenital heart defects, airway malformations, and inborn errors of metabolism are less common etiologies. Clinicians should be familiar with updated neonatal resuscitation guidelines. Initial evaluation includes a detailed history and physical examination. The clinician should monitor vital signs and measure oxygen saturation with pulse oximetry, and blood gas measurement may be considered. Chest radiography is helpful in the diagnosis. Blood cultures, serial complete blood counts, and C-reactive protein measurement are useful for the evaluation of sepsis. Most neonates with respiratory distress can be treated with respiratory support and noninvasive methods. Oxygen can be provided via bag/mask, nasal cannula, oxygen hood, and nasal continuous positive airway pressure. Ventilator support may be used in more severe cases. Surfactant is increasingly used for respiratory distress syndrome. Using the INSURE technique, the newborn is intubated, given surfactant, and quickly extubated to nasal continuous positive airway pressure. Newborns should be screened for critical congenital heart defects via pulse oximetry after 24 hours but before hospital discharge. Neonatology consultation is recommended if the illness exceeds the clinician's expertise and comfort level or when the diagnosis is unclear in a critically ill newborn.