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The potential impact of renal replacement therapy on clinical outcomes in acute renal failure (ARF) remains a subject of ongoing investigation and controversy. This article reviews in depth the clinical trials to date that have examined the effect of dialysis-related variables on outcomes of patients with hospital-acquired ARF. In particular, the role of the dialysis modality, dialyzer characteristics, and dosing strategies are discussed. Clinical trials comparing intermittent hemodialysis (HD) to continuous renal replacement therapies (CRRT) have failed to demonstrate a survival difference when adjusting for disease severity. Similarly, studies evaluating dialyzer membrane biocompatibility and flux properties had no impact on survival. Efforts aimed at measuring dialysis adequacy in patients with ARF receiving HD using urea kinetic modeling are hindered by a lack of understanding of solute kinetics in this setting. However, dosing strategies during CRRT are promising. Finally, the application of cell therapy to the successful substitution of renal function shows promise for the future.