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For more than 40 years, noninvasive ventilation has been the first-line preferred therapy for acute-on-chronic conditions, such as COPD and cardiogenic pulmonary edema. The use of noninvasive ventilation in the treatment of hypoxemic respiratory failure, however, has been met with mixed results associated with higher risks of intubation (failure of therapy) and with higher risks of mortality. The purpose of this review was to describe the current evidence and important considerations when patients with hypoxemic respiratory failure are managed with noninvasive ventilation.