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High-flow nasal cannula (HFNC) is emerging as a means of oxygen delivery and respiratory support for a range of conditions outside the perinatal period. We aim to review the mechanisms of action and advantages of HFNC and to summarize current findings regarding clinical benefit in specific pediatric disease processes and in patients with significant respiratory distress.Currently published studies outside the neonatal population demonstrate both safety and efficacy of this mode of respiratory support. Retrospective and prospective observational trials have shown improvements in oxygenation and respiratory distress, as well as reductions in the need for intubation in select patient populations. Randomized controlled trials are ongoing.HFNC is emerging as a means of oxygen delivery and respiratory support across a wide range of pediatric conditions. Available data suggest that it is well tolerated by children and can have a favorable effect on clinical outcomes. Future research will better define optimal patient populations and best practices for use.