Combining advances in proton accelerator research and molten salt reactor concepts tested by Oak Ridge National Laboratory, accelerator driven subcritical reactors (ADSR) have the potential to enhance nuclear safety, waste management, and global nonproliferation. ADSR systems, such as GEM*STAR, hold a number of inherent safety features—subcritical operations, continuous removal of fission products, and molten salt fuel. Use of ADSRs can also further spent fuel management objectives through the destruction of higher actinides and long-lived radionuclides. In addition to producing electricity, ADSR process heat can be utilized to produce synthetic diesel fuels, improving the economics of such systems. While ADSRs are currently being promoted as an alternative means for plutonium disposition under international disarmament obligations, future applications include playing crucial roles in innovative fuel cycles and the reuse of spent nuclear fuel. Nevertheless, the development of an ADSR prototype and overcoming political barriers restricting access to spent fuel material will be critical in ensuring the widespread deployment of such systems.