The incremental diagnostic value of integrated positron emission tomography-computed tomography (PET/CT) or single-photon emission computed tomography (SPECT)/CT images compared with PET or SPECT alone, or PET or SPECT correlated with a CT obtained at a different time includes the following: (1) improvement in lesion detection on both CT and PET or SPECT images, (2) improvement in the localization of foci of uptake resulting in better differentiation of physiological from pathologic uptake, (3) precise localization of the malignant foci, for example, in the skeleton vs soft tissue or liver vs adjacent bowel or node (4) characterization of serendipitous lesions, and (5) confirmation of small, subtle, or unusual lesions. The use of these techniques can occur at the time of initial diagnosis, in assessing the early response of disease to treatment, at the conclusion of treatment, and in continuing follow-up of patients. PET/CT and SPECT/CT fusion images affect the clinical management in a significant proportion of patients with a wide range of diseases by (1) guiding further procedures, (2) excluding the need of further procedures, (3) changing both inter- and intramodality therapy, including soon after treatment has been initiated, and (4) by providing prognostic information. PET/CT fusion images have the potential to provide important information to guide the biopsy of a mass to active regions of the tumor and to provide better maps than CT alone to modulate field and dose of radiation therapy. It is expected that the role of PET/CT and SPECT/CT in changing management will continue to evolve in the future and that these tools will be fundamental components of the truly "personalized medicine" we are striving to deliver.