The morbidity and mortality associated with respiratory failure is, to a certain extent, iatrogenic. Mechanical ventilation, although the mainstay of treatment for respiratory distress syndrome, can result in physical trauma to lung tissue (ventilator-induced lung injury [VILI]). Strategies to alleviate VILI are often termed lung-protective strategies and are aimed at reducing overstretching and shear stresses associated with repetitive alveolar collapse and reopening. Lower tidal volumes during ventilation, maintenance of positive-end expiratory pressure, and high-frequency ventilation are the best-studied lung-protective strategies that appear to reduce VILI. Faster withdrawal from mechanical ventilation could also improve outcomes and lower the costs associated with care. To enhance the success of weaning from mechanical ventilation, the cooperative efforts of physicians and respiratory therapists are needed. These efforts involve the initiation of spontaneous-breathing trials, implementation of systematic weaning protocols, and optimization of individual patient interventions.