Various types of ionizing radiation may be used therapeutically for benign skull base tumors. Treatment may involve single-dose radiosurgery, or may be fractionated into multiple doses. Designing and implementing a radiotherapy plan that maximizes the therapeutic ratio requires knowledge of the biophysical and radiobiological principles involved in these treatments. These basic radiobiological tenets are discussed in this chapter, with the focus on radiotherapy of benign skull base tumors. Animal and clinical data, however, acquired from the radiation of malignant tumors are necessarily included, as they comprise much of our knowledge of fractionation schedules, central nervous system (CNS) toxicity, and CNS volume effects.