Bronchopulmonary dysplasia affects thousands of infants annually with high attendant morbidity, mortality, and healthcare costs. Respiratory outcomes for preterm infants may be widely disparate even within the same medical center for infants of similar gestational ages. Given the high estimates for the heritability for bronchopulmonary dysplasia as measured at 36 weeks of postmenstrual age, the course of disease for a particular infant is likely heavily influenced by factors that operate prenatally or in the early postnatal period. In this review we discuss the etiologies of lung disease in the premature infant, including in utero, genetic, and epigenetic factors that may influence pulmonary outcomes.