Radiographic contrast material-induced nephropathy (RCIN) is the third most common cause of hospital-acquired renal insufficiency and has been associated with an increase in patient mortality Many strategies to prevent RCIN have been explored unsuccessfully. The standard of care remains hydration with 0.45% sodium chloride before and after administration of contrast material. Recently, N-acetylcysteine and fenoldopam have been studied to determine their efficacy in preventing RCIN. Of seven prospective studies using various dosing regimens of N-acetylcysteine, four revealed beneficial results. Although some discrepancies exist, the data strongly suggest that N-acetylcysteine has a role in patients at risk for the development of RCIN. The data for fenoldopam are more limited, with only one retrospective study showing benefit. Additional prospective data are required to determine if fenoldopam has a role in the prevention of RCIN.