Since 1978, the ANS biennial topical conference on Probabilistic Safety Assessment has been a worldwide forum for communication of major probabilistic risk and safety topics, including issues, methods, applications, insights, policy, research, and risk-informed regulation experience. PSA 2021 will be of interest to those working in traditional applications such as nuclear reactor facilities, nonreactor installations, processing, decontamination & decommissioning, storage as well as other nontraditional areas where probabilistic safety approaches are applied. Topics of discussion are anticipated to include small modular reactor (SMR), Fukushima Dai-ichi, advanced reactor, multiunit and full site PSA, waste cleanup, natural phenomena, security, and fire risk, as well as security, fire risk, and more.. The role of probabilistic methods in understanding uncertainties and improving the safety and security of nuclear facilities and activities will be highlighted. In assessing nuclear power plant risk, traditional PSA methods will need to change to address NPP designs with substantially different safety profiles. In the Licensing Modernization Project, a risk-informed approach has been developed by the Nuclear Energy Institute for assessing regulatory compliance of new reactor designs with a risk limit curve. New tools based on artificial intelligence are under development for interpreting data that will aid in the characterization of risk. Another focus of the conference will be to delineate the issues facing PSA and how these issues can be addressed. The theme of this year’s PSA conference is to look forward to the future of PSA for NPPs and outward at non-nuclear disciplines to address the evolution of risk-management for a spectrum of societal issues. The first two days of the conference will primarily address risk management issues associated with broader societal and allied industry (chemical, aerospace, automotive, medical risks). The lessons learned from the application of PSAs to risk management will be discussed along with how these lessons can be applied to non-nuclear applications. The last three days will focus on NPP PSA issues as in past PSA conferences but with particular emphasis on development needs.