Ionizing radiation is a powerful tool to treat cancer. The curing effect is mainly based on the efficiency of ionizing radiation to kill the cancer cells and it is believed that DNA double-strand breaks (DSBs) represent the most significant genetic lesion introduced by radiation that causes cell killing. One limitation in radiotherapy is the unavoidable damage delivered to the normal, noncancer cells that can give rise to side effects. The ultimate goal in treatment planning is to maximize cell killing in the tumor by minimizing damage induction in the normal tissue surrounding the tumor. The biological response to the induction of DSBs is largely affected by DSB repair processes and it has, therefore, been a long-standing goal to determine a patient's DSB repair capacity to “individualize” treatment planning. A recently developed DSB repair assay that allows the assessment of patients' repair capacity under in vivo conditions may provide a new approach to predict individuals' responses to radiotherapy and may be able to contribute to improvements in treatment planning. © 2006 Wiley-Liss, Inc.