Disclosed are hemodialysis and similar dialysis systems including fluid flow circuits. Hemodialysis systems may include a blood flow path, and a dialysate flow path including balancing, mixing, and/or a directing circuits. Preparation of dialysate may be decoupled from patient dialysis. Circuits may be defined within one or more cassettes. The fluid circuit and/or the various fluid flow paths may be isolated from electrical components. A gas supply may be provided that, when activated, is able to urge dialysate through the dialyzer and blood back to the patient. Such a system may be useful during a power failure. The hemodialysis system may also include fluid handling devices, such as pumps, valves, mixers, etc., actuated using a control fluid. The control fluid may be delivered to the fluid handling devices using a detachable external pump. The fluid handling devices may have a spheroid shape with a diaphragm dividing it into two compartments.