Described are fluid pumping and fluid handling systems, which may be suitable for use in medical devices, such as artificial or extracorporeal blood pumping systems. The systems can include a dual housing configuration for pneumatic actuation comprising a main housing containing a pump cassette comprising a pneumatically actuated pump and pneumatically actuated valves. The pump can include a pump actuation chamber and pump pneumatic port, and the valves can each include a valve actuation chamber and valve pneumatic port. Connecting tubes can be used to fluidly connect the pump actuation ports and valve actuation ports to a tube-support housing having a first side receiving one end of each connecting tube and a second side providing a pneumatic interface arranged to connect to an array of pneumatic receptacles on a base unit of the system to facilitate easy, compact and accurate pneumatic interconnection between the pump cassette and the base unit.