Conventional, thrice-weekly hemodialysis (CHD) is the most commonly prescribed dialysis regimen. Despite widespread acceptance of CHD, long-term analyses of registry data have revealed an increased risk for mortality during the long 2-day interdialytic interval of thrice-weekly therapies. High mortality rates during this period suggest that there may be a role for more frequent HD in improving patient outcomes and survival through elimination of the long interdialytic period. Several regimens have been investigated including: short, daily HD, frequent nocturnal HD, and alternate-day HD. In this review, we provide an in-depth summary of current data comparing the effects of frequent and CHD modalities on survival, hospitalizations, vascular access complications, burden of therapy, quality of life, residual renal function, cardiovascular parameters, bone mineral metabolism, and anemia. Limitations of the data as well as the role of frequent dialysis in clinical practice are also discussed.