The availability of (99m)Tc for single-photon imaging in diagnostic nuclear medicine is crucial, and current availability is based on the (99)Mo/(99m)Tc generator fabricated from fission-based molybdenum (F (99)Mo) produced using high enriched uranium (HEU) targets. Because of risks related to nuclear material proliferation, the use of HEU targets is being phased out and alternative strategies for production of both (99)Mo and (99m)Tc are being evaluated intensely. There are evidently no plans for replacement of the limited number of reactors that have primarily provided most of the (99)Mo. The uninterrupted, dependable availability of (99m)Tc is a crucial issue. For these reasons, new options being pursued include both reactor- and accelerator-based strategies to sustain the continued availability of (99m)Tc without the use of HEU. In this paper, the scientific and economic issues for transitioning from HEU to non-HEU are also discussed. In addition, the comparative advantages, disadvantages, technical challenges, present status, future prospects, security concerns, economic viability, and regulatory obstacles are reviewed. The international actions in progress toward evolving possible alternative strategies to produce (99)Mo or (99m)Tc are analyzed as well. The breadth of technologies and new strategies under development to provide (99)Mo and (99m)Tc reflects both the broad interest in and the importance of the pivotal role of (99m)Tc in diagnostic nuclear medicine.