The pathology of BPD has changed over time, with the old BPD characterized by airway injury, inflammation, and parenchymal fibrosis giving way to the new BPD manifesting less fibrosis but with decreased alveolar and vascular development. The pathogenesis of BPD involves factors affecting the severity and management of RDS, alterations in lung development and maturation, alveolar-vascular interactions, and extracellular matrix remodeling. These factors in pathogenesis are mediated and modulated by hyperoxic lung injury, antioxidants, NO, the pulmonary neuroendocrine system and peptide growth factors, the immune system, and various genetic polymorphisms and predispositions. Future therapeutic interventions are likely to target one or more of these abnormalities in lung development, maturation, and response to injury.