In the late seventies, iodinated contrast agents (ICA) were considered to be a major cause of acute iatrogenic renal failure. Over the last decade new contrast agents have been synthesized, nonionic and less hyperosmolar. Analysis of 25 series published between 1975 and 1989 does not allow precise evaluation of the incidence of acute renal failure due to ICAs. This incidence varies from 3.7 to 70% of cases according to the series, with an average figure of 10.2%. Such discrepancies stem from different definitions of renal failure, as well as varying criteria adopted for defining "nephrotoxicity", high-risk patients and the better safety of new, nonionic and less hyperosmolar agents. The pathophysiology of ICA nephrotoxicity was mainly studied in laboratory animal models. Three main factors are involved in an inducing ICA-mediated decrease in glomerular filtration rate: reduction of the renal plasma flow, a direct cytotoxic effect on renal tubular cells and erythrocyte alteration leading to intrarenal sludge. Excluding dysglobulinemias with urinary excretion of immunoglobulin light chains, which represent a special case of maximum nephrotoxicity, 4 main risk factors of renal toxicity have been identified in nondiabetic subjects: previous renal failure with serum creatinine levels greater than 140 mumol per liter, extracellular dehydration, age over 60 and use of high doses of ICA and/or repeated ICA injections before serum creatinine levels return to baseline. Diabetes does not seem to represent a serious risk factor, except in patients with diabetic glomerulosclerosis. Ongoing treatment with nonsteroidal antiinflammatory drugs (NSAID) potentiates the hazards of renal failure. Preventive measures for avoiding ICA nephrotoxicity are threefold: maintain or restore adequate hydration with saline infusion, stop NSAID treatment several days before ICA administration, and allow a 5 day interval before repeating contrast media injections. New, nonionic and moderately hyperosmolar contrast agents appear to be much less nephrotoxic than conventional ICAs in laboratory animals and in high-risk patients. It is advisable to select such contrast media for investigating high-risk patients. This approach was recently substantiated in well designed, randomized clinical studies which included more than 2,000 patients.