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A resurgence of interest in noninvasive mechanical ventilation to treat patients with acute or chronic respiratory failure is mainly an attempt to avoid complications commonly associated with the presence of an artificial airway when providing conventional positive-pressure ventilation. Although noninvasive ventilation via noninvasive positive-pressure ventilation has largely supplanted negative ventilation as a form of noninvasive ventilation, negative-pressure ventilation still has an active role in patients who require ventilatory assistance but who cannot tolerate noninvasive positive-pressure ventilation. In some centers throughout Europe, negative-pressure ventilation is used to treat acute respiratory decompensation due to chronic obstructive pulmonary disease, neurologic disorders, or neonates suffering with respiratory distress syndrome. In this review, we discuss the details of applying negative-pressure ventilation and explore the physiologic effects of negative-pressure ventilation on gas exchange, upper airway function, cardiovascular performance, and lower esophageal sphincter tone. Finally, we discuss the application of negative-pressure ventilation in specific disease states including neonatal respiratory distress syndrome, a variety of neuromuscular diseases, and in patients with chronic obstructive pulmonary disease.