The indications for initiation of renal replacement therapy in acute renal failure are controversial. Although volume overload, metabolic acidosis, hyperkalemia and other electrolyte disturbances, and overt uremic manifestations are commonly accepted indications for renal replacement therapy, specific criteria for initiation of therapy based on these conditions are highly subjective. Progressive azotemia in the absence of overt uremia is another common indication for renal replacement therapy although there is no consensus on the degree of azotemia that warrants initiation of therapy. The clinical data regarding timing and initiation of renal support in patients who have acute renal failure are reviewed. Definitive resolution of the appropriate indications and timing for initiation of renal replacement therapy in acute renal failure requires prospective evaluation in a randomized clinical trial.