Acute renal failure (ARF), induced by either toxins or ischemia, is associated with significant morbidity. The pathogenesis of ARF is complex and is characterized by renal vasoconstriction and oxidative stress in association with tubular and microvascular injury and interstitial inflammation. In many situations, ARF is associated with a rise in serum uric acid as a result of both increased generation and decreased excretion. Although it is widely recognized that markedly elevated levels of uric acid can cause ARF via supersaturation within the tubules with crystallization and intrarenal obstruction ("acute urate nephropathy"), the possibility that uric acid may affect renal outcomes at concentrations that do not lead to tubular obstruction have not been considered. This article reviews both the salutary and the adverse effects of uric acid on biologic processes and presents the hypothesis that hyperuricemia, particularly if chronic and marked, likely represents a true risk factor for ARF. Hyperuricemia also may account for the paradoxic lack of benefit of diuretics in the management of ARF. It is suggested that studies are needed to investigate the role of chronic hyperuricemia on renal outcomes after acute tubular injury.