Recent studies in the treatment of acute respiratory failure in children have been targeted at reducing ventilator-induced lung injury, providing treatment adjuncts to mechanical ventilation, and assessing innovative therapies directed at immunomodulation. Ventilator-associated lung injury has been demonstrated in animal models during the delivery of moderate-to-large tidal volumes and has also been described in adult populations. Subsequently, a significant survival benefit of a low tidal volume, high positive end expiratory pressure strategy on the ventilatory was found in adults. Investigation of the effects of inhaled nitric oxide in acute respiratory failure patients continues to show transient improvements in oxygenation, but no evidence of improved outcomes. The use of intratracheal surfactant within 24 hours of intubation in pediatric respiratory failure may be beneficial in reducing the days of mechanical ventilation. Neutrophil oxidative damage has been demonstrated, but therapies directed at decreasing neutrophil adherence have failed to demonstrate improvements. Enteral anti-inflammatory and antioxidant therapy may be promising, because these modalities have been shown to improve a number of surrogate outcomes in patients with respiratory failure. The use of corticosteroids in the late stages of lung injury has also recently been shown to have promise.