Radioisotopes are used worldwide in a range of medical, industrial, research and academic applications. A large proportion of these radioisotopes are produced in particle accelerators and the number of institutions that operate linear accelerators or cyclotrons and manufacture and distribute radiopharmaceuticals, for example, is significant and increasing. The production of radioisotopes using particle accelerators poses significant radiation hazards to workers, members of the public, and the environment when accelerators are operated without adequate radiation safety measures. This Safety Guide provides practical guidance for implementing radiation protection and safety measures in such facilities involved in the production and use of radioisotopes.