PET/CT, the most common form of hybrid imaging, has transformed oncologic imaging and is increasingly being used for nononcologic applications as well. Performing PET/CT in children poses unique challenges. Not only are children more sensitive to the effects of radiation than adults but, following radiation exposure, children have a longer postexposure life expectancy in which to exhibit adverse radiation effects. Both the PET and CT components of the study contribute to the total patient radiation dose, which is one of the most important risks of the study in this population. Another risk in children, not typically encountered in adults, is potential neurotoxicity related to the frequent need for general anesthesia in this patient population. Optimizing pediatric PET/CT requires making improvements to both the PET and the CT components of the procedure while decreasing the potential for risk. This can be accomplished through judicious performance of imaging, the use of recommended pediatric 18fluorine-2-fluoro-2-deoxy-d-glucose (18F-FDG) administered activities, thoughtful selection of pediatric-specific CT imaging parameters, careful patient preparation, and use of appropriate patient immobilization. In this article, we will review a variety of strategies for radiation dose optimization in pediatric 18F-FDG-PET/CT focusing on these processes. Awareness of and careful selection of pediatric-specific CT imaging parameters designed for appropriate diagnostic, localization, or attenuation correction only CT, in conjunction with the use of recommended radiotracer administered activities, will help to ensure image quality while limiting patient radiation exposure. Patient preparation, an important determinant of image quality, is another focus of this review. Appropriate preparative measures are even more crucial in children in whom there is a higher incidence of brown fat, which can interfere with study interpretation. Finally, we will discuss measures to improve the patient experience, the resource use, the departmental workflow, and the diagnostic performance of the study through the use of appropriate technology, all in the context of minimizing procedure-related risks.