Because of its low density, the He/O2 mixture markedly affects the dynamics of gas-flow, increasing inspiratory and expiratory flows, reducing WOB and respiratory acidosis, and relieving dyspnea in various clinical situations associated with obstructive airway disease. The magnitude of these changes varies according to the proportion of turbulent, transitional, and laminar flow conditions. These effects, however, last only as long as the patient breathes the He/O2 mixture, because it has no curative effect on the cause of airway obstruction. Thus, He/O2 ventilation is mostly useful while awaiting the effects of more definitive treatment. Evidence shows that He/O2 ventilation can improve pathophysiologic and clinical parameters in spontaneously breathing patients with upper airway obstruction, asthma. COPD, bronchopulmonary dysplasia. and bronchiolitis. Furthermore. He/O2 ventilation may prove to be a valuable adjunct in decompensated COPD patients, during both NIV and conventional mechanical ventilation. Despite promising results, however, there are two primary pitfalls to He/O2 ventilation. First, the consequences of the physical properties of the He/O2 mixture on various ventilator functions, the major differences between machines, and the correction factors to apply (if necessary) should be known. Second, in this age of cost control, particular attention should be paid to the cost-benefit ratio of He/O2 ventilation. Indeed, despite clinical evidence that the pathophysiologic principles on which He/O2 ventilation rests can be translated into favorable short-term physiologic and subjective effects, there is presently no evidence of a significant effect on patient outcome. Hence, before He/O2 ventilation can be recommended for widespread use, prospective outcome studies should be conducted in patients who suffer from the conditions discussed in this article to identify which, if any, are most likely to receive a benefit. Meanwhile, the authors recommend that He/O2 ventilation be reserved for patients who have a severe condition and who do not respond to the classic validated treatment modalities.