The role of positron emission tomography (PET) during the past decade has evolved rapidly from that of a pure research tool to a methodology of enormous clinical potential. (18)F-fluorodeoxyglucose (FDG)-PET is currently the most widely used probe in the diagnosis, staging, assessment of tumor response to treatment, and radiation therapy planning because metabolic changes generally precede the more conventionally measured parameter of change in tumor size. Data accumulated rapidly during the last decade, thus validating the efficacy of FDG imaging and many other tracers in a wide variety of malignant tumors with sensitivities and specificities often in the high 90 percentile range. As a result, PET/computed tomography (CT) had a significant impact on the management of patients because it obviated the need for further evaluation, guided further diagnostic procedures, and assisted in planning therapy for a considerable number of patients. On the other hand, the progress in radiation therapy technology has been enormous during the last two decades, now offering the possibility to plan highly conformal radiation dose distributions through the use of sophisticated beam targeting techniques such as intensity-modulated radiation therapy (IMRT) using tomotherapy, volumetric modulated arc therapy, and many other promising technologies for sculpted three-dimensional (3D) dose distribution. The foundation of molecular imaging-guided radiation therapy lies in the use of advanced imaging technology for improved definition of tumor target volumes, thus relating the absorbed dose information to image-based patient representations. This review documents technological advancements in the field concentrating on the conceptual role of molecular PET/CT imaging in radiation therapy treatment planning and related image processing issues with special emphasis on segmentation of medical images for the purpose of defining target volumes. There is still much more work to be done and many of the techniques reviewed are themselves not yet widely implemented in clinical settings.