A hemodialysis system, the system comprising: a blood pump including a peristaltic pump actuator; a dialyzer; a blood cassette including a pumping line that is operatively connected to the peristaltic pump actuator of the blood pump such that the blood pump can pump blood through the blood cassette when the blood cassette is in fluid communication with a blood source, the blood cassette including a rigid housing, a flexible membrane operable with the rigid housing, a plurality of ports including a from-patient port, a to-patient port, a saline port, a to-dialyzer port, and a from-dialyzer port defined by the rigid housing, an air separation chamber defined by the rigid housing, and a plurality of valve seats (28x, 28y, 28z) defined by the rigid housing to control blood and dialysate flow; a dialysate pump including a peristaltic pump actuator; an ultrafiltration pump including a peristaltic pump actuator; a dialysate cassette separate from the blood cassette, the dialysate cassette operatively connected to the dialysate pump such that the dialysate pump can pump dialysate through the dialysate cassette by actuation of a first pumping tube of the dialysate cassette when the dialysate cassette is in fluid communication with the dialysate source, the dialysate cassette being fluidly connected to the dialyzer and operatively connected to the ultrafiltration pump such that the ultrafiltration pump can pump used dialysate through the dialysate cassette via actuation of a second pumping tube, the dialysate cassette including a rigid housing and a flexible membrane (74a, 74b, 74c) operable with the rigid housing, two balance chambers (50a, 50b) for controlling the flow of dialysate, a supply line, a drain line, a to-dialyzer line, a from-dialyzer line and an inline fluid heating pathway defined within the flexible membrane, wherein the first pumping tube, the second pumping tube, the supply line, the to-dialyzer line, the from-dialyzer line, and the drain line are held at least in part by a tubing organizer; and a dialysis machine having a first machine portion configured with the blood pump to receive the blood cassette and a second machine portion configured with the dialysate pump to receive the dialysate cassette. a blood pump including a peristaltic pump actuator; a dialyzer; a blood cassette including a pumping line that is operatively connected to the peristaltic pump actuator of the blood pump such that the blood pump can pump blood through the blood cassette when the blood cassette is in fluid communication with a blood source, the blood cassette including a rigid housing, a flexible membrane operable with the rigid housing, a plurality of ports including a from-patient port, a to-patient port, a saline port, a to-dialyzer port, and a from-dialyzer port defined by the rigid housing, an air separation chamber defined by the rigid housing, and a plurality of valve seats (28x, 28y, 28z) defined by the rigid housing to control blood and dialysate flow; a dialysate pump including a peristaltic pump actuator; an ultrafiltration pump including a peristaltic pump actuator; a dialysate cassette separate from the blood cassette, the dialysate cassette operatively connected to the dialysate pump such that the dialysate pump can pump dialysate through the dialysate cassette by actuation of a first pumping tube of the dialysate cassette when the dialysate cassette is in fluid communication with the dialysate source, the dialysate cassette being fluidly connected to the dialyzer and operatively connected to the ultrafiltration pump such that the ultrafiltration pump can pump used dialysate through the dialysate cassette via actuation of a second pumping tube, the dialysate cassette including a rigid housing and a flexible membrane (74a, 74b, 74c) operable with the rigid housing, two balance chambers (50a, 50b) for controlling the flow of dialysate, a supply line, a drain line, a to-dialyzer line, a from-dialyzer line and an inline fluid heating pathway defined within the flexible membrane, wherein the first pumping tube, the second pumping tube, the supply line, the to-dialyzer line, the from-dialyzer line, and the drain line are held at least in part by a tubing organizer; and a dialysis machine having a first machine portion configured with the blood pump to receive the blood cassette and a second machine portion configured with the dialysate pump to receive the dialysate cassette.