Research suggests daily hemodialysis may improve clinical outcomes. To date, a comprehensive review of its implications on quality of life has not been performed, and little is known about its economic impact. We conducted an economic evaluation comparing short daily or nocturnal hemodialysis with thrice-weekly conventional in-center dialysis. Data on the quality of life and clinical effects of daily dialysis were obtained from more than 60 reports from 13 daily dialysis programs around the world (n = 197). Cost data were derived principally from the US Renal Data System, Centers for Disease Control, and Medicare Payment Advisory Commission. Resource use during daily hemodialysis was modeled after two ongoing programs in the United States. Results suggest that patients feel better and direct treatment costs could be reduced with daily dialysis. Costs are sensitive to assumptions about the effect of daily dialysis on hospital days. Reductions of at least 8% in hospital days are required for these modalities to be cost saving compared with documented reductions of 30% to 100%. Larger well-controlled studies of daily versus conventional dialysis would be helpful to determine whether daily dialysis fulfills these promises. Medicare policy, which limits payment for most patients to three dialysis treatments weekly, poses a disincentive to more widespread adoption among dialysis centers. Given this constraint to broader acceptance, we address several policy options to gain a better understanding of the potential risks and benefits of daily dialysis.