Considerable effort has been devoted to the development of strategies to reduce the incidence of bronchopulmonary dysplasia (BPD), including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent BPD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia, were evaluated for the improvement of other outcomes and found to reduce BPD. Cohort studies suggest that the use of continuous positive airway pressure as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce BPD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7-11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease.