Target definition is a major source of errors in both prostate and head and neck external-beam radiation treatment. Delineation errors remain constant during the course of radiation and therefore have a large impact on the dose to the tumor. Major sources of delineation variation are visibility of the target including its extensions, disagreement on the target extension, and interpretation or lack of delineation protocols. The visibility of the target can be greatly improved with the use of multimodality imaging. Both in the head and neck and the prostate, computed tomography (CT)-magnetic resonance imaging coregistration decreases the target volume and its variability. CT-positron emission tomography delineation is promising for delineation in head and neck cancer. Despite the better visibility, a different interpretation of the target extension remains a major source of error. The use of coregistration of CT with a second modality, together with improved guidelines for delineation and an online anatomical atlas, increases agreement between observers in prostate, lung, and nasopharynx tumors. Delineation errors should not be treated differently from other geometrical errors. Similar margin recipes for the correction of setup errors and organ motion should be adapted to incorporate the effect of delineation errors. A calculation of a 3-dimensional clinical target volume-planning target volume margin incorporating delineation errors for the head and neck is around 6.1 to 9.7 mm. Given the good local control of IMRT with smaller margins and smaller pathological specimens, it is likely that the delineated CTV frequently overestimates the actual volume.