As a technical support organization for French Public Authorities, the Institute for Radioprotection and Nuclear Safety (IRSN) shall participate in policy making on nuclear safety and radiation protection. In the framework of its current activity, the IRSN performs analysis and comparison of different safety assessment approaches, including Best Estimate Plus Uncertainty (BEPU), among others. Although BEPU is not yet recognized worldwide, the authors consider it a promising way to stimulate the involvement of a new generation of numerical tools and high-fidelity experiment data for nuclear safety assessment and development of nuclear technology. This paper discusses enabling factors and constraints for BEPU from technical and global points of view, relying on scientific background as well as current practice with respect to its potential role in regulation and, more generally, in a decision-making process.