A hemodialysis system is disclosed. The hemodialysis system includes a dialyzer and an online dialysate generation system comprising a water inlet line and a drain line. The hemodialysis system also includes a disposable set comprising a supply tube fluidly connected to online dialysate generation system and a dialysate pumping tube fluidly connected to the dialyzer. The hemodialysis system further includes a dialysis instrument comprising a dialysate pump head and a motor positioned and arranged to operate the dialysate pump head. The dialysis instrument operates the dialysate pump head to move fresh dialysate from the online dialysate generation system through the dialysate pumping tube to the dialyzer.