Combined positron emission tomography and computed tomography (PET/CT) has proven clinical utility, particularly in the diagnosis, staging, and management of cancer. The use of PET/CT has grown substantially in the past few years, with an increasing number of hospitals and imaging centers installing PET/CT systems each year. The combination of 2 procedures, which each imparting a radiation dose and hence the potential for deleterious health effects, creates unique radiation safety issues. This article addresses the radiation safety issues posed by PET/CT with regard to the protection and safety of PET/CT personnel, the public, and adult and pediatric patients.