Elaborating upon the requirements on periodic safety reviews that are established in IAEA Safety Standards Series No. SSR-4, Safety of Nuclear Fuel Cycle Facilities, this publication aims to provide practical information on conducting the periodic safety review for a nuclear fuel cycle facility by the operating organization, and on the regulatory review and assessment of the periodic safety review. The publication covers the planning and preparation for periodic safety review, use of a graded approach, review of safety factors, global assessment of the safety of the facility and development of an implementation plan to address the findings of the periodic safety review.