The field of radiation oncology has evolved, especially in the past 20 years. Advances in technology, particularly in computing power, software, and imaging, have fueled contributions to cancer care. It is currently fashionable to say that many of these advances have only served to increase costs of care without clear evidence of benefit, and certainly, efforts to evaluate the value of radiation oncology treatments are needed. However, it is undeniable that the future of radiation oncology depends on discovering such advances and to demonstrate that these increase the therapeutic index of treatment. Across the global radiation oncology community, investigations are proceeding in which innovative means are being used to achieve this goal. We review some of these novel methods to improve the therapeutic index of radiation therapy.