Increased knowledge of the pathophysiologic mechanisms of impaired gas exchange during acute respiratory failure during recent years has stimulated many studies that evaluate different treatments to improve oxygenation and outcome. Changes in body position (mainly prone positioning) can significantly improve gas exchange in patients with acute respiratory distress syndrome and acute lung failure, with few complications related to the maneuver; however, no survival advantage has yet been detected. A correlation between aerated lung tissue and oxygenation also confirms the importance of recruitment maneuvers in improving gas exchange. Recent suggestions that recruitment of alveoli proceeds during most of the inspired vital capacity and not only around the lower inflection point of the pressure-volume curve raises the question how to best perform recruitment maneuvers. New data support the hypothesis that maintenance of even small amount of spontaneous breathing during mechanical ventilation (with airway pressure release ventilation or biphasic positive airway pressure) can improve gas exchange, whereas other unconventional ventilatory modes have not yet proved advantageous. Some mechanisms responsible for the high percentage of nonresponse to inhaled nitric oxide have recently been proposed, and combinations of inhaled nitric oxide with other therapies have been tested. Increased knowledge in this area may, in the future, make inhaled nitric oxide more attractive in the treatment of adult respiratory failure as well as in neonatal intensive care.