NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.