Hemodialysis dialysis systems are disclosed. Hemodialysis systems of the invention may include a dialysate flow path including a balancing circuit, a mixing circuit, and/or a directing circuit. The circuits may be defined within one or more cassettes. The fluid circuits may be at least partially isolated, spatially and/or thermally, from electrical components of the system. A gas supply may be provided in fluid communication with the dialysate flow path and/or the dialyzer to urge dialysate through the dialyzer and blood back to the patient. The hemodialysis systems may include fluid handling devices, actuated using a control fluid, optionally delivered using a detachable pump. Fluid handling devices may be generally rigid and of a spheroid shape, optionally with a diaphragm dividing the device into compartments.