In recent years ibuprofen has been proposed for the treatment of patent ductus arteriosus (PDA) as it has been proved to be equally as effective as indomethacin and shows fewer cerebral blood flow, intestinal and renal hemodynamic effects. A number of studies and several meta-analyses comparing both drugs are now available that debate whether indomethacin or ibuprofen should be used for PDA prophylaxis or closure. This review examines the available knowledge on the specific issue of the effects of ibuprofen on kidney function, as improved renal tolerance is a major argument in favor of its use in the routine treatment of PDA. There is sufficient evidence to consider that ibuprofen, at the currently proposed dosing regimen, has a similar efficacy to indomethacin but is better tolerated by the neonatal kidney when employed for the treatment of established PDA. However, adverse effects of ibuprofen have been evidenced both in trials on the use of ibuprofen for the prevention of PDA and of intraventricular hemorrhage-periventricular hemorrhage (IVH-PVH), and in experimental studies on a neonatal, anesthetized animal model. Thus ibuprofen, as with other cyclooxygenase (COX) inhibitors, may not be exempt from causing renal adverse effects, especially in circumstances when renal prostaglandin activation is maximal (i.e., when administrated early after birth, in more immature patients and in certain situations such as in the anesthetized rabbit). However, although the issue has been addressed extensively in the last decades, there is insufficient evidence that therapeutic intervention in PDA is beneficial in terms of mortality or clinically significant morbidity outcomes. Studies aimed at resolving this key issue are still needed.