Radioisotopes make important contributions in various sectors of economic significance including medicine, food processing, industry, agriculture and research. Radioisotope handling facilities may be upgraded for production of radiopharmaceuticals, radioisotope generators and radioactive sources, and for medical and industrial applications. Handling of radioactivity needs special facilities to shield the radiation emitted and to prevent contamination of the environment. In addition, radioisotopes for medical applications must comply with GMP requirements. The automation of radioisotope handling facilities for various operations in hot cells such as target handling, radiochemical processing, radiopharmaceuticals manufacturing, dispensing or autoclaving is crucial. Radioisotope handling facilities that are optimized to significantly reduce radiation dose and increase GMP compliance are elaborated upon in this publication.