Contrast-induced nephropathy (CIN) is a leading cause of iatrogenic acute kidney failure. Periprocedural CIN results in a greater risk of requiring renal replacement therapy, prolonged hospitalization, excessive health care costs, potential long term kidney impairment and mortality. Identified risk factors for CIN include premorbid chronic kidney disease, diabetes mellitus, congestive heart failure, critical illness and volume of administered contrast media. Prophylactic interventions for the prevention of CIN remain controversial and uncertain. In this review we critically appraise the evidence for prevention of CIN. In general, every attempt should be made to correct underlying volume depletion, discontinue potential nephrotoxins, reverse any acute kidney dysfunction or when not possible, consider delay of procedure or an alternative modality for imaging. A minimum volume of contrast media should be employed, including going left ventriculogram and performing staged procedures if applicable. There are few interventions with quality evidence for reducing the incidence of CIN. procedure hydration and the use of nonionic iso-osmolar contrast media have consistently demonstrated efficacy. For patients at high risk, there is evidence to suggest benefit with N-acetylcysteine. Clinical studies with adenosine antagonists are encouraging; however, further confirmatory trials are required. Based on the available studies, there is inadequate evidence for the routine use of hemofiltration, atrial natriuretic peptides, calcium channel blockers, or prostaglandins. There is no evidence to support prophylaxis with diuretic therapy, forced diuresis, low dose dopamine, fenoldopam, captopril, or endothelin receptor antagonists. Despite recent advances in the epidemiology, pathophysiology and natural history of CIN, few effective prophylactic or therapeutic interventions have conclusively demonstrated evidence for a reduction in CIN incidence and no therapy has proven efficacious once CIN is established.