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Contrast nephropathy (CN) accounts for significant morbidity and mortality. Patients with pre-existing renal insufficiency, especially those with diabetic nephropathy, are at particular risk. Medullary hypoxia due to decreased renal blood flow and direct cytotoxicity contribute to the pathogenesis. Contrast nephropathy is usually defined as an increase in serum creatinine concentration >0.5 mg/dl or 25% above the baseline level within 48 h. Intravenous hydration (saline 0.45%, if tolerated 0.9% at a rate of 1 ml/kg/h) 12 h before and after contrast exposure and the use of low or iso-osmolality contrast agents are advisable. The benefit of low-dose dopamine as well as the selective dopamine-1 receptor agonist fenoldopam is unproven. Studies on the effectiveness of the adenosine antagonist theophylline have led to conflicting results. Because theophylline has a narrow therapeutic range and may be associated with adverse effects, it is not a prophylactic agent of first choice. The administration of N-acetylcysteine (NAC) has been evaluated in several trials with inconsistent results. Newer data suggest a benefit of high-dose NAC (1,200 mg twice daily) for patients receiving high doses (>140 ml) of contrast agent, or those with advanced renal insufficiency (creatinine >2.5 mg/dl). Whereas prophylactic hemodialysis does not prevent CN, a recent study demonstrated a marked benefit of prophylactic hemofiltration.