Acute hypoxic respiratory failure (AHRF) remains a significant cause of death in intensive care units. With the realization that pathophysiologic abnormalities in AHRF involve surfactant abnormalities as well as inflammatory and vascular changes, it is not surprising that nitric oxide (NO) has been investigated as an adjunct to the multiple ventilatory strategies adopted in the management of this disorder. Since the enthusiastic reports of Roussaint in 1993 showing improved survival with inhaled NO in the management of AHRF, several well-designed studies have been published, all designed to investigate the utility of NO in neonatal, pediatric and adult patients. Michael Schreiber and colleagues evaluated 207 preterm infants with AHRF in a randomized, double-blind placebo-controlled study. Inhaled NO was administered at a constant low dose for up to 6 days in the NO group. Patients were further randomized to conventional ventilation and to high-frequency oscillatory ventilation. The patients showed a statistically significant improvement in their primary endpoint of the incidence of chronic lung injury and death in the inhaled NO group. There was no increase in the incidence of intraventricular hemorrhage between the study and placebo groups. Schreiber and colleagues concluded that early treatment with inhaled NO would improve long-term pulmonary outcomes in premature infants with respiratory distress syndrome, decreasing the incidence of chronic lung disease and death. Prior to this study no prospective randomized trial had demonstrated any benefits in clinical outcomes such as the length of hospital stay or death. This study supports the belief that the majority of patients will experience, at a minimum, a short-term benefit from inhaled NO therapy, but also suggests that inhaled NO may influence clinical outcomes as well. The recognition that AHRF is often the result of a multifactorial process makes it unlikely that one treatment modality will have a major beneficial effect on mortality and morbidity.