The mechanism most likely responsible for the development of radiocontrast nephropathy (RCN) is contrast-induced renal tubular ischemia. At this time, intravenous hydration remains the mainstay for preventing RCN. The antihypertensive agent fenoldopam has been shown in a canine model, as well as in small, retrospective, prospective, and randomized human evaluations, to be effective for preventing RCN. In addition, studies have reported the ability of the free radical scavenger N-acetylcysteine (NAC) to prevent RCN. The clinical trial data for NAC, however, are not consistent regarding this effect, which, if present, appears to be modest and perhaps restricted to lower-risk clinical scenarios.