During fetal life, the ductus arteriosus (DA) acquires the mechanisms for its postnatal closure following a thorough developmental program. This program can be interrupted by preterm birth and is also susceptible to alteration during fetal life by numerous physiological and pathological stimuli. In this review, we aim to summarize the evidence on how physiological and pathological factors affect DA development, eventually leading to patent DA (PDA). Specifically, we reviewed the associations of sex, race, and pathophysiological pathways leading to very preterm birth (endotypes) with PDA incidence and pharmacological closure. Summary of evidence suggests that there are no male-female differences in the incidence of PDA among very preterm infants. In contrast, risk of developing PDA appears to be higher in infants exposed to chorioamnionitis or who are small for gestational age. Finally, hypertensive disorders of pregnancy may be associated with a better response to pharmacological treatment of PDA. All of this evidence comes from observational studies and therefore associations do not imply causation. The current trend for many neonatologists is to wait for the natural evolution of preterm PDA. Continued research is needed to identify which fetal and perinatal factors modulate the eventual late closure of PDA in very and extremely preterm infants.