Thin chamber diaphragm-operated fluid handling devices, including thin chamber pumps and thin chamber valves, facilitate device compactness and, in some configurations, self-priming. Diaphragm actuators of the thin chamber devices either comprise or are driven by piezoelectric materials. The thinness of the chamber, in a direction parallel to diaphragm movement, is in some embodiments determined by the size of a perimeter seal member which sits on a floor of a device cavity, and upon which a perimeter (e.g. circumferential or peripheral portion) of the diaphragm actuator sits. The diaphragm actuator is typically retained in a device body between the floor seal member and another seal member between which the perimeter of the actuator is sandwiched. The devices have an input port and an output port.