This Safety Guide provides recommendations and guidance on conducting periodic safety review (PSR) of an existing nuclear power plant. PSR is a comprehensive safety review of all important aspects of safety, carried out at regular intervals, typically every ten years. In addition, PSR may be used in support of the decision making process for licence renewal or long term operation, or for restart of a nuclear power plant following a prolonged shutdown. The review process described in this Safety Guide is valid for nuclear power plants of any age and may have a wider applicability, for example to research reactors and radioactive waste management facilities, by means of a graded approach. Although PSR may not be an appropriate means for identifying safety issues in the decommissioning phase, the documentation resulting from PSR of an operating nuclear power plant will be an important input when planning decommissioning.