Clinical studies have demonstrated that hybrid single photon emission computed tomography (SPECT)/CT for various diagnostic issues has an added value as compared to SPECT alone. However, the combined acquisition of functional and anatomical images can substantially increase radiation exposure to patients, in particular when using a hybrid system with diagnostic CT capabilities. It is, therefore, essential to carefully balance the diagnostic needs and radiation protection requirements. To this end, the evidence on health effects induced by ionizing radiation is outlined. In addition, the essential concepts for estimating radiation doses and lifetime attributable cancer risks associated with SPECT/CT examinations are presented taking into account both the new recommendations of the International Commission on Radiological Protection (ICRP) as well as the most recent radiation risk models. Representative values of effective dose and lifetime attributable risk are reported for ten frequently used SPECT radiopharmaceuticals and five fully diagnostic partial-body CT examinations. A diagnostic CT scan acquired as part of a combined SPECT/CT examination contributes considerably to, and for some applications even dominates, the total patient exposure. For the common SPECT and CT examinations considered in this study, the lifetime attributable risk of developing a radiation-related cancer is less than 0.27 %/0.37 % for men/women older than 16 years, respectively, and decreases markedly with increasing age at exposure. Since there is no clinical indication for a SPECT/CT examination unless an emission scan has been indicated, the issue on justification comes down to the question of whether it is necessary to additionally acquire a low-dose CT for attenuation correction and anatomical localization of tracer uptake or even a fully diagnostic CT. In any case, SPECT/CT studies have to be optimized, e.g. by adapting dose reduction measures from state-of-the-art CT practice, and exposure levels should not exceed the national diagnostic reference levels for standard situations.