In preterm infants, a left-to-right patent ductus arteriosus (PDA) shunt can decrease systemic blood pressure; decrease brain, intestine, and kidney blood flows; increase pulmonary blood flow, pressure, and edema; and alter pulmonary mechanics. A PDA is also associated with several serious neonatal morbidities, like pulmonary hemorrhage, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and neurodevelopmental disabilities. Whether PDA-induced hemodynamic changes contribute to the associated neonatal morbidities and whether early PDA treatment before clinical symptoms develop can improve neonatal outcomes are questions that have confounded neonatologists for the last 50 years.