Acute renal failure (ARF) occurs in up to 30% of patients who undergo cardiac surgery, with dialysis being required in approximately 1% of all patients. The development of ARF is associated with substantial morbidity and mortality independent of all other factors. The pathogenesis of ARF involves multiple pathways. Hemodynamic, inflammatory, and nephrotoxic factors are involved and overlap each other in leading to kidney injury. Clinical studies have identified risk factors for ARF that can be used to determine effectively the risk for ARF in patients who undergo bypass surgery. These high-risk patients then can be targeted for renal protective strategies. Thus far, no single strategy has demonstrated conclusively its ability to prevent renal injury after bypass surgery. Several compounds such as atrial natriuretic peptide and N-acetylcysteine have shown promise, but large-scale trials are needed.