This Safety Guide provides recommendations on how to meet the requirements of IAEA Safety Standards Series No. SSR-2/1 (Rev. 1), Safety of Nuclear Power Plants: Design, in relation to fuel handling and storage systems. The publication addresses the design aspects of handling and storage systems for fuel that remain part of the operational activities of a nuclear reactor. It covers the following stages of fuel handling and storage in a nuclear power plant: receipt, storage and inspection of fresh fuel before use and transfer of fresh fuel into the reactor; removal of irradiated fuel from the reactor and transfer of the irradiated fuel to the spent fuel pool; and reinsertion of irradiated fuel from the spent fuel pool into the reactor. Recommendations are also provided on the storage, inspection and repair of irradiated or spent fuel in the spent fuel pool, and the preparation for the removal of this fuel from the spent fuel pool and on the handling of fuel casks in the spent fuel pool and on their transfer.