The field of radiation oncology is rapidly evolving especially thanks to the tremendous progress in robotics and computer sciences. One of the consequences is the implementation of a technique like the CyberKnife. This particular radiation therapy modality allows the use of "ablative" radiation doses, a concept which is not even conceivable with conventional approaches. This has been made possible by major changes in the ways target and margins around are defined and the way radiation therapy is fractionated. The result of these changes is for some tumours a doubling of the radiobiological effect of the ionizing irradiation. In order to cover the target with the highest possible conformality, without harming surrounding healthy tissues, optimized definition of the target is key. It is not only important to get information on the extent of the target with the highest possible resolution, but it is also important to assess the content, i.e., metabolic heterogeneity. The developments made in the field of diagnostic and functional radiology and nuclear medicine do allow to take advantage of the numerical information to individualize and adapt treatment prescription, even consider modification throughout the course of irradiation.