Nuclear medicine will play an increasingly important role in medicine due to its increasingly personalized approach. Important radionuclides used for diagnostics (Tc-99m) and targeted therapies (Y-90, I-131, Sm-153, Ho-166, Lu-177, Re-188), as well as for brachytherapy (Co-60, I-125, Ir-192) are currently produced by nuclear reactors. Although cyclotrons can produce complementary radionuclides, and further research can result in alternative routes for several reactor-produced radionuclides, it will not be sufficient to make nuclear reactors redundant in the next few decades. However, the aging of the main reactors involved in global supply of medical radionuclides makes secure radionuclide supply difficult. To prevent new and more frequent medical radionuclide shortages, a shared global responsibility is needed by (nuclear) medicine, nuclear industry, and politics, which should lead to replacement of a small number of aging reactor facilities. It should be taken into account that dedicated production reactors are not economically viable, if the full cost recovery principle defined by the OECD-NEA applies. The replacement projects should go hand in hand with up-scaling projects of most promising alternative radionuclide production routes, preferably under the auspices of an international entity to make nuclear medicine less vulnerable to shortages.