A variety of therapeutic approaches have been used both to prevent acute ischemic and nephrotoxic renal injury and to improve renal function and reduce mortality once acute renal failure (ARF) has developed. Unfortunately, there have been few rigorous assessments of the efficacy of these treatment interventions. The reasons for the lack of abundant critical data regarding treatment effects in ARF are several. First, ARF is a functional disorder. It has a spectrum of etiologies, occurs in a variety of clinical settings and varies in severity. Second, selected endpoints of treatment success vary and co-morbid factors frequently determine outcome. Third, it had been difficult to carry out prospective controlled studies in a disorder in which the mortality rate approaches 50%. In this review, an effort was made to analyze the available literature with a primary focus on controlled studies to determine significant prophylactic and treatment effects of various interventions in ARF. Three endpoints of therapy (change in renal function, change in course of azotemia, and change in mortality) were examined for pharmacologic agents. Changes in course of azotemia and mortality were assessed in evaluating different dialysis modes. Effect on nitrogen balance, change in course of azotemia, and change in mortality were used as endpoints to determine treatment effects of different nutritional regimens. When weight was given to prospective controlled studies, some insights emerged as to treatment interventions that are most likely to have beneficial effects in specific settings of ARF. Among pharmacologic agents, mannitol appears to have a positive prophylactic effect in kidney transplantation. There are no other significant beneficial effects of diuretics for prophylaxis or as treatment in early or established ARF. Of vasoactive agents, there is a relatively small amount of data suggesting that diltiazem may have a positive prophylactic effect in kidney transplantation, and dopamine possibly is beneficial early in the evolutionary phase of ARF. Atrial natriuretic peptide and calcium channel blockers may have beneficial effects in established disease. No other pharmacologic interventions are supported by substantial data. At best, the results are equivocal regarding the use of early and vigorous dialysis in ARF. However, there are recent impressive data indicating that the use of biocompatible membranes is efficacious in recovery and survival. There is no clear evidence that one form of nutritional therapy has advantages over others, but some level of amino acid supplementation in addition to basic energy replacement is supported by the overall data.