This paper discusses a number of the key challenges to the acceptance and application of probabilistic risk analysis (PRA). Those challenges include: (a) the extensive reliance on subjective judgment in PRA, requiring the development of guidance for the use of PRA in risk-informed regulation, and possibly the development of “robust” or “reference” prior distributions to minimize the reliance on judgment; and (b) the treatment of human performance in PRA, including not only human error per se but also management and organizational factors more broadly. All of these areas are seen as presenting interesting research challenges at the interface between engineering and other disciplines.