An increase in the length of the standard in-center hemodialysis treatment by 30 to 45 minutes per session was not associated with an improvement in mortality in long-term hemodialysis patients enrolled in the HEMO study. Testing the possibility that delivering still higher doses of hemodialysis may have a beneficial effect on patient outcomes will require the use of more frequent hemodialysis or a much longer duration for each dialysis session. "Short-daily hemodialysis," actually 6 times per week hemodialysis for 1.5 to 3 hours per session, can provide some increase in small molecule clearance as measured by urea kinetics. "Long nocturnal daily hemodialysis," actually 6 times per week hemodialysis for 6 to 8 hours per session, provides a significant increase in both small-molecular-weight and large-molecular-weight clearance and often alleviates the need to take phosphate binders. The National Institutes of Health is sponsoring 2 clinical trials via the Frequent Hemodialysis Network to determine the impact of these 2 modalities on intermediate outcomes, compared with standard 3-times-per-week hemodialysis.