Hypoxemia may be treated with either low-flow nasal cannula or high-flow nasal cannula. The first method has its limitations, as maximum FiO2 of 0.45 can be administered. The latter method allows for oxygen supplementation where not only 100% oxygen can be delivered, but, additionally, positive airway pressure improves end-expiratory lung volumes. High-flow oxygen therapy has earned its place in various clinical settings including treatment of hypoxemia in the course of acute hypoxemic respiratory failure and cardiogenic pulmonary edema. It is also used in the operating room as a pre-oxygenation method before endotracheal intubation. In the intensive care units, it is applied after extubation in patients who have low risk of intubation within the next 7 h following extubation. Air flow, humidification, temperature and FiO2 can be titrated independently based on the patient’s respiratory demand, tolerance, and cause of respiratory distress.