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Functional imaging with positron emission tomography (PET) is playing an increasingly important role in the diagnosis and staging of malignant disease, image-guided therapy planning, and treatment monitoring. PET with the labeled glucose analogue fluorine 18 fluorodeoxyglucose (FDG) is a relatively recent addition to the medical technology for imaging of cancer, and FDG PET complements the more conventional anatomic imaging modalities of computed tomography (CT) and magnetic resonance imaging. CT is complementary in the sense that it provides accurate localization of organs and lesions, while PET maps both normal and abnormal tissue function. When combined, the two modalities can help both identify and localize functional abnormalities. Attempts to align CT and PET data sets with fusion software are generally successful in the brain; other areas of the body is more challenging, owing to the increased number of degrees of freedom between the two data sets. These challenges have recently been addressed by the introduction of the combined PET/CT scanner, a hardware-oriented approach to image fusion. With such a device, accurately registered anatomic and functional images can be acquired for each patient in a single scanning session. Currently, over 800 combined PET/CT scanners are installed in medical institutions worldwide, many of them for the diagnosis and staging of malignant disease and increasingly for monitoring of the response to therapy. This review will describe some of the most recent technologic developments in PET/CT instrumentation and the clinical indications for which combined PET/CT has been shown to be more useful than PET and CT performed separately.