Besides its direct effects to kill tumor cells, radiotherapy was recognized to have potent immunostimulatory properties that contribute to the development of anti-cancer immune response. Radiotherapy was reported to induce various pro-immunogenic and phenotypic changes in malignant cells, and recalibrated the immune background of the tumor microenvironment, leading to activation of the innate immune system and triggering tumor-specific T cell immunity. The immune dependence of radiotherapy provides a rational for the development of combination therapy, whereby the immunomodulatory properties of radiation can be utilized to enhance the activity of immunotherapy. Recently successful strategies, such as immunological checkpoint blockade, and extensive experimental data demonstrated the efficacy of the combination of radiotherapy and immunotherapy. The clinical potential of this approach is currently being explored in a number of clinical trials. A successful combination requires careful consideration of the most appropriate radiation dose and fractionation, as well as immunotherapy options. The immune control of cancer is now becoming a clinical reality. It is quite optimistic that effective combination of radiotherapy and immunotherapy can induce long-term systemic immunity, which will further enhance the patient’s therapeutic effect and change the future management of cancer.