Abstract: A dialysis machine is disclosed that incorporates a water treatment module, a dialysate preparation module having a dialysate circuit, and an extracorporeal circuit including a dialyzer and arterial and venous blood lines that connect to the patient. The machine accomplishes on-line disinfection of all the fluid circuits of the machine, including the water treatment module, the dialysate preparation module and extracorporeal circuit, the arterial and venous lines, and the dialyzer, by circulating water heated to a high level disinfection temperature (e.g., 80 degrees C.) through the fluid passages of the machine for a sufficient time (such as an hour) to achieve high level disinfection. After the dialysis session is ended, the patient connects the arterial and venous lines to ports in a disinfection manifold that places the arterial and venous lines into fluid communication with the heated water. Thereafter, the machine is ready to disinfect the fluid circuits including the extracorporeal circuit.