This publication is a revision of IAEA Safety Standards Series No. NS-R-2, Safety of Nuclear Power Plants: Operation, and has been extended to cover the commissioning stage. It describes the requirements to be met to ensure the safe commissioning, operation, and transition from operation to decommissioning of nuclear power plants. Over recent years there have been developments in areas such as long term operation of nuclear power plants, plant ageing, periodic safety review, probabilistic safety analysis review and risk informed decision making processes. It became necessary to revise the IAEA’s Safety Requirements in these areas and to correct and/or improve the publication on the basis of feedback from its application by both the IAEA and its Member States. In addition, the requirements are governed by, and must apply, the safety objective and safety principles that are established in the IAEA Safety Standards Series No. SF-1, Fundamental Safety Principles. A review of Safety Requirements publications, initiated in 2011 following the accident in the Fukushima Daiichi nuclear power plant in Japan, revealed no significant areas of weakness but resulted in a small set of amendments to strengthen the requirements and facilitate their implementation. These are contained in the present publication.