Acute respiratory failure in infants is usually a single system lung disease. Despite this, the optimal technique for ventilating the surfactant-deficient premature newborn continues to be the subject of clinical investigations. Studies have yet to demonstrate what the optimal lung recruitment strategy is, both in terms of level of mean airway pressure and the duration of sustained inflations. There is further evidence that the inflammatory nature of chronic lung disease of prematurity can be moderated by systemic steroid therapy, although the optimal dose has yet to be worked out. In older children, in whom lung disease is frequently part of a multisystem disorder, it has proved difficult to show improved outcomes with lung-targeted therapy. Randomized trials of inhaled nitric oxide and surfactant therapy have not shown improved survival despite improvements in physiologic parameters.