The marquee cell of the immune response, the T lymphocyte, is exquisitely sensitive to ionizing radiation. Moreover, the majority of cells of the hematopoietic lineage, with their high turnover and radiation sensitivity, are effectively ablated by relatively low radiation doses, such that total-body irradiation is an effective immunosuppressive therapy. Despite and sometimes because of these facts, the immune system may underlie some portion of the therapeutic effects of radiation. In this review, we will discuss these processes, and go on to discuss current therapies combining radiation therapy with immunotherapy for the treatment of cancer.