High-resolution, three-dimensional functional imaging has improved delivery of radiotherapy to tumors while minimizing damage to adjacent, healthy tissue. A growing array of energy sources and delivery systems, including external delivery of protons and brachytherapy, are also credited with improvement in the therapeutic index of treating diseases with radiation. In many malignancies, the therapeutic effects of radiotherapy can be significantly augmented by coordinated delivery of adjunctive therapies, particularly chemotherapy. In age-related macular degeneration (AMD) and other diseases of the eye, radiotherapy combined with pharmaceutical agents, including antiangiogenesis therapies, have the potential to an additive or synergistic effect. In AMD, the most significant challenge for radiotherapy may be precise delivery to the target and avoidance of damage to surrounding tissues.