The nasal cannula has been a commonly used patient interface to provide supplemental oxygen since its introduction in the 1940s. Traditionally, it has been categorized as a low-flow device and capable of delivering a 0.4 F(IO(2)) with flows up to 6 L/min to adults with normal minute ventilation. However, there is considerable performance variability among patients and design, which results in an exponential decline in delivered F(IO(2)) as breathing frequencies increase. The nasal cannula has also been successfully adapted for use in perinatal and pediatric respiratory care; flows are reduced, in the range of 0.25-1 L/min, due to smaller minute volumes. A decade or so ago, high-flow nasal cannula (HFNC) oxygen therapy was introduced, accompanied by heated humidification systems to prevent the associated drying of upper airway mucosa and to increase patient comfort. Therapeutic flows for adults were in the 15-40 L/min range; F(IO(2)) could be independently adjusted with air/O(2) blending. The HFNC has also found additional clinical application in perinatal care, as delivery systems with flows > 2 L/min could create a distending pressure similar to nasal CPAP. There is a small but growing body of information from clinical trials that supports use of HFNC as an alternative oxygen interface for adults who present with moderate hypoxemia that persists after receiving oxygen by reservoir-bag masks or similar therapy. Clinical observations report greater patient acceptance and comfort versus oxygen masks. HFNC therapy has also been considered valuable in perinatal care in treating the respiratory distress syndrome or supporting patients after extubation similar to nasal CPAP. At present, research-based evidence for the role of HFNC for its perinatal applications remains unclear. This review will identify proposed mechanisms for therapeutic effectiveness, current delivery equipment, guidelines for rational patient application, and direction for further research.