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Currently the U.S. is sponsoring production of radioisotope thermoelectric generators (RTGs) for the Cassini mission to Saturn; the SP-100 space nuclear reactor power system for NASA applications; a thermionic space reactor program for DoD applications as well as early work on nuclear propulsion. In an era of heightened public concern about having successful space ventures it is important that a full understanding be developed of what it means to “flight qualify” a space nuclear system. As a contribution to the ongoing work this paper reviews several qualification programs, including the general-purpose heat source radioisotope thermoelectric generators (GPHS-RTGs) as developed for the Galileo and Ulysses missions, the SNAP-10A space reactor, the Nuclear Engine for Rocket Vehicle Applications (NERVA), the F-1 chemical engine used on the Saturn-V, and the Space Shuttle Main Engines (SSMEs). Similarities and contrasts are noted.