A medical fluid flow control system is described. In one embodiment, the system comprises: an interface including a pump actuator port and a pump seal port; a membrane gasket including a pump actuation area and a pump aperture; and a pumping cassette including a flexible sheet and defining a pump chamber, a pump portion of the flexible sheet covering the pump chamber. The pump seal port is operable with the pump aperture to seal the pump portion of the flexible sheet to the pump actuation area of the membrane gasket and the pump actuator port is configured to move the pump portion of the flexible sheet and the pump actuation area of the membrane gasket at the pump chamber of the cassette. In another embodiment, the system comprises: an interface including a valve actuator port and a valve seal port; a membrane gasket including a valve actuation area and a valve aperture; and a pumping cassette including a flexible sheet and defining a valve chamber, a valve portion of the flexible sheet covering the valve chamber. The valve seal port is operable with the valve aperture to seal the valve portion of the flexible sheet to the valve actuation area of the membrane gasket and the valve actuator port is configured to move the valve portion of the flexible sheet and the valve actuation area of the membrane gasket at the valve chamber of the cassette.