Positron emission tomography (PET) and PET/computed tomography (CT) with the glucose analog (18)F-fluorodeoxyglucose (FDG) are increasingly used to assess response to therapy in patients, and there is converging evidence that changes in glucose utilization during therapy can be used to predict clinical outcome. Today, integrated PET/CT systems have mainly replaced stand-alone PET devices, providing the opportunity to integrate morphologic information and functional information. However, the use of PET/CT systems also gives rise to methodological challenges for the quantitative analysis of PET scans for treatment monitoring. Recently published single-center studies demonstrate that FDG-PET and FDG-PET/CT have been successfully used for monitoring of tumor response to cytotoxic therapy in a variety of tumor entities. The potential early identification of nonresponding tumors provides an opportunity to alter treatment regimens according to the individual chemosensitivity of the tumor tissue. In this article, we review the methodological background to monitoring of cancer treatment with PET/CT, the diagnostic and prognostic performance of PET/CT for predicting tumor response with the glucose analog FDG in various tumor entities, and the clinical potential of new imaging probes. In addition, the future direction of research and clinical applications is discussed.