Targeting a localized tumor with radiation therapy remains a logical option following relapse recurrence or following a second primary diagnosis. However, factors that essentially determine the use of treatment do not depend on feasibility. Rather, the clinical benefits versus risks, supported by scientific data, should provide further information to the clinician for making the optimal decision for treatment. Reirradiation therefore must weigh the risks associated with normal tissue damage against the associated probability of tumor control. The use of radiation therapy and normal tissue effects of radiation to such therapy has not changed, but the volume of normal tissue being irradiated during initial therapy has been reduced with the use of more conformal techniques. A decision to offer reirradiation should always be made on a personalized basis after detailed discussion with the patient on expected benefits versus risk of increased late morbidities. A multidisciplinary approach is highly recommended as the perceived risk–benefit ratio is complex and requires detailed case by case analysis. Many factors can influence the decision for reirradiation.