Many of the ongoing and expected uses of Probabilistic Safety Assessment (PSA)(1) create new challenges to ensuring that the resulting conclusions are valid. This paper provides a summary of some of these challenges. Work conducted by the authors on Risk-informed Inservice Inspection (RI-ISI) is used to illustrate these challenges. Means to address all of the challenges are not provided in detail in this paper. Several earlier papers discuss how these challenges can be addressed. References are provided for the interested reader (Chapman JR et al. In: PSA '95, vol. 1, Seoul, 1995: 177-80; Chapman TR et al. In: ICONE-IV, New Orleans, 1996; Dimitrijevic VB et al. In: Croatian Nuclear Society International Conference, Opatija, 1996: 245-54; Dimitrijevic VB et al. In: Croatian Nuclear Society International Conference, Opatija, 1996: 255-62; Dimitrijevic VB. In: Yugoslav Nuclear Society Conference, Belgrade, 1996. 53-61; O'Regan PJ et al. In: PSA '95, Seoul, vol. 1, 1995. 403-5; O'Regan PJ. In: ICONE-IV, vol. 5, New Orleans, 1996: 277-80). (C) 1999 Elsevier Science Ltd. AU rights reserved.