Based on the progress made during the last few years in understanding the pathophysiology of acute renal failure, a plethora of therapeutic drug and nondrug interventions have been developed and tested in animal and human forms of this disease. The first part of this article focuses on the role of volume expansion and vasopressors in the prevention and treatment of acute renal failure in the critically ill. From all prophylactic measures that have been proposed, volume expansion, or at least correction of volume depletion, remains the most efficient and most evidence-based intervention in these patients. Norepinephrine is, out of all the vasopressors, probably the most appropriate to use in cases of hypotension, provided circulating volume is adequate. In hypotensive septic patients, vasopressin has been shown to be useful. Direct renal vasodilating substances, the most popular still being low-dose dopamine, have never been proved to be useful in carefully performed prospective trials. Moreover dopamine especially is associated with a number of side effects and complications. From the agents acting on tubular factors, the diuretic mannitol and loop diuretics are the most prescribed. Only in specific situations such as rhabdomyolysis and kidney transplant surgery has it been shown that mannitol was able to prevent acute renal failure. The loop diuretics are able, after establishing adequate circulating volume, to promote diuresis in some forms of oliguric acute renal failure; however, some recent papers have shown that the administration of loop diuretics may actually be associated with increased mortality and delayed recovery of renal function. The last few years have seen a number of trials with acetylcysteine in the prevention of mainly radiocontrast nephropathy. Although the results are still conflicting, the majority indicates that acetylcysteine, when applied together with adequate volume expansion, may be a useful drug to incorporate in the standard treatment procedures in patients at risk for acute renal failure. Interventions to stimulate the recovery process of the damaged kidney with growth factors, although theoretically sound, have thus far not led to successful results.