In vivo and in vitro labeled leukocytes have been shown to be very effective in detecting different infectious and inflammatory conditions. The model of labeled leukocyte imaging is based on the powerful mechanisms of chemotaxis exerted on activated leukocytes by chemo-attractants. The avidity of inflammatory cells for fluorodeoxyglucose (FDG) has led to the concept of labeling leukocytes with [(18F)]FDG ex vivo. This concept combines cell-bound radionuclide trafficking from the blood pool compartment to the lesion with the high resolution of positron emission tomography (PET) imaging. The further benefits of having a correlated anatomical map by implementing the acquisition on a hybrid PET/computed tomography (CT) device are obvious. The feasibility and the potential value of leukocyte PET(/CT) imaging in infection have been demonstrated. The available data suggest a high accuracy of the method. Still, leukocyte PET/CT should not be considered as the endpoint of infection imaging, since it only meets a part of the criteria of the ideal infection imaging agent. However, the common clinical need for specific detection of infection with anatomical precision, the availability of the components necessary for performing leukocyte PET/CT, their lack of toxicity or adverse effects and the absence of more superior tracers on the commercial market make it worthwhile to further investigate leukocyte PET/CT imaging in larger prospective series. The advantages of leukocyte PET/CT over the more conventional nuclear medicine and radiological methods makes this imaging tool likely to be useful in certain subsets of infected patients.