Extremely premature neonates born at the canalicular to saccular stage of lung development (22–28 wk of gestation) are at very high risk of developing bronchopulmonary dysplasia (BPD). The premature lung, now having to complete lung development in the extrauterine environment, is subjected to many adverse exposures, including hyperoxia, that promote the development of BPD. Many developmental pathways are precisely orchestrated for optimal lung maturation. Decreased or sustained activation of these pathways may contribute to the pathogenesis of this disease or may impair recovery of the lung from injury. Identification of these novel pathways and their mediators is crucial for the establishment of mechanisms leading to BPD and the development of novel therapeutic strategies.