Four major challenges are facing the long-term development of nuclear energy: improvement of the economic competitiveness, meeting increasingly stringent safety requirements, adhering to the criteria of sustainable development, and public acceptance. Meeting the sustainability criteria is the driving force behind the topic of this paper. In this context, sustainability has two aspects: natural resources and waste management. IAEA's activities in the area of Partitioning and Transmutation (P&T) are mostly in response to the latter. While not involving the large quantities of gaseous products and toxic solid wastes associated with fossil fuels, radioactive waste disposal is today's dominant public acceptance issue. In fact, small waste quantities permit a rigorous confinement strategy, and mined geological disposal is the strategy followed by some countries. Nevertheless, political opposition arguing that this does not yet constitute a safe disposal technology has largely stalled these efforts. One of the primary reasons cited is the long life of many of the radioisotopes generated from fission. This concern has led to increased R&D efforts to develop a technology aimed at reducing the amount and radio-toxicity of long-lived radioactive waste through transmutation in fission reactors or sub-critical systems. In the frame of the Project on Technology Advances in Fast Reactors and Accelerator-Driven Systems (ADS), the IAEA initiated a number of activities on utilization of plutonium and transmutation of long-lived radioactive waste, ADS, and deuterium–tritium plasma-driven sub-critical systems. The paper presents past accomplishments, current status and planned activities of this IAEA project.