Nanomaterials have been shown to have physical and chemical properties that have opened new avenues for cancer diagnosis and therapy. Nanoconstructs that enhance existing treatments for cancer, such as radiation therapy, are being explored in several different ways. Two general paths toward nanomaterial-enabled radiosensitization have been explored: (1) improving the effectiveness of ionizing radiation and (2) modulating cellular pathways leading to a disturbance of cellular homeostasis, thus rendering the cells more susceptible to radiation-induced damage. A variety of different agents that work via one of these two approaches have been explored, many of which modulate direct and indirect DNA damage (gold), radiosensitivity through hyperthermia (Fe), and different cellular pathways. There have been many in vitro successes with the use of nanomaterials for radiosensitization, but in vivo testing has been less efficacious, predominantly because of difficulty in targeting the nanoparticles. As improved methods for tumor targeting become available, it is anticipated that nanomaterials can become clinically useful radiosensitizers for radiation therapy.