A hemodialysis system for operation with a blood source and a dialysate source, the system including: (i) a first machine portion including a blood pump; (ii) a blood cassette operatively connected to the blood pump such that the blood pump can pump blood through the blood cassette when the blood cassette is in fluid communication with the blood source; (iii) a dialyzer fluidly connected to the blood cassette; (iv) a second machine portion separate from the first machine portion, the second machine portion including a dialysate pump; and (v) 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 when the dialysate cassette is in fluid communication with the dialysate source, the dialysate cassette being fluidly connected to the dialyzer.