PET/MRI as a hybrid modality provides novel imaging opportunities. Although there is a very broad array of diseases that could benefit from PET/MRI, there is only a narrow range of applications for which the benefit over standard care justifies the higher resource use and, in particular, offers a net positive trade-off over PET/CT. This benefit is generally associated with the omission of CT and the associated radiation dose from the patient workup. This article summarizes the generally accepted clinical applications of PET/MRI in both adult and pediatric populations. Although there are several potential applications and certainly exciting research that may expand applications in the future, the purpose of this paper was to focus on current, mainstream applications. This is the final article in a 4-part integrated series sponsored by the PET/MR and Publication Committees of the Society of Nuclear Medicine and Molecular Imaging–Technologist Section.