This Safety Guide provides recommendations on safety in the siting, design, construction, commissioning, operation and preparation for the decommissioning of nuclear fuel research and development facilities to meet the relevant requirements established in IAEA Safety Standards Series No. SSR-4, Safety of Nuclear Fuel Cycle Facilities. It applies to all types of nuclear fuel cycle research and development facility, including facilities involving small scale experiments, analyses and fundamental research studies on the chemical, physical, mechanical and radiological properties of specific materials such as prototype nuclear fuels (before and after reactor irradiation) and investigations of nuclear materials and wastes arising from new processes, and facilities involving research and development on processes and equipment envisaged for use on an industrial scale (e.g. pilot facilities for waste treatment). This publication is intended for operating organizations and designers of nuclear fuel cycle research and development facilities and relevant technical support organizations and regulatory bodies.