Cardiovascular disease remains the leading cause of morbidity and mortality for patients with end-stage renal disease (ESRD). Frequent intensive hemodialysis (short daily hemodialysis [2 hours per session, six sessions per week] and nocturnal home hemodialysis [6 hours per session, five to six sessions per week]) has recently gained increasing popularity as an alternative to conventional hemodialysis (4 hours per session, three sessions per week). There is an emerging body of evidence that frequent intensive hemodialysis offers superior uremic toxin clearance, blood pressure control, and other cardiovascular outcomes. The goals of the present review are to systematically evaluate the available evidence in blood pressure control and cardiovascular outcomes in ESRD and the achievable changes after converting from conventional dialysis to frequent intensive hemodialysis, and to provide possible physiological explanations to account for these important changes of potent markers of adverse events in this patient population.