Patent ductus artteriosus (PDA) often complicates the clinical course of neonates born prematurely and increases their short- and long-term morbidity. Treatment of PDA remains an ongoing debate among neonatologists for various issues such as the timing, the criteria and the methods for its closure. Non steroidal anti inflammatory drugs have been used as the standard pharmacological treatment for PDA. Indomethacin was the first one to be used. Its use though, waned due recognition of renal cerebral and gastrointestinal complications associated with the administration of this drug. Ibuprofen has emerged in clinical practice, as it has been reported to have lower nephrotoxicity. This review will examine existing data in the literature on the early- and long-term nephrotoxicity associated with the two drugs and will discuss present and future directions the management and prevention of this condition.