The ductus arteriosus (DA) is a vessel whose patency is required for fetal survival but is incompatible with postnatal life. Because of developmental insufficiency, the DA in preterm infants often fails to close in a condition known as patent DA (PDA). Although COX inhibitors can be used to close the PDA by lowering circulating prostaglandin levels, their effectiveness is correlated with birth weight, and severely premature infants often require surgical repair. Paradoxically, targeted deletion of COX pathway components in mice results in PDA. In this issue of the JCI, Yokoyama et al. describe dual roles for prostaglandins in DA development and closure, offering new insights into the mechanism of negative effects of COX inhibitors that may influence the treatment of severely premature infants with PDA and lead to improvement of their outcomes (see the related article beginning on page 3026).