High-frequency oscillatory ventilation (HFOV) is an established mode of respiratory support in the neonatal intensive care unit. Large clinical trial data is based on first intention use in preterm infants with acute respiratory distress syndrome. Clinical practice has evolved from this narrow population. HFOV is most often reserved for term and preterm infants with severe, and often complex, respiratory failure not responding to conventional modalities of respiratory support. Thus, optimal, and safe, application of HFOV requires the clinician to adapt mean airway pressure, frequency, inspiratory:expiratory ratio and tidal volume to individual patient needs based on pathophysiology, lung volume state and infant size. This narrative review summarises the status of HFOV in neonatal intensive care units today, the lessons that can be learnt from the past, how to apply HFOV in different neonatal populations and conditions and highlights potential new advances. Specifically, we provide guidance on how to apply an open lung approach to mean airway pressure, selecting the correct frequency and use of volume-targeted HFOV.