An anti-tumor immune response is one of the most important factors that can determine treatment response and prognosis of cancer patients. Recent studies have demonstrated that radiotherapy can activate tumor-specific immune responses and that these responses contribute to the therapeutic efficacy. However, the exact mechanisms underlying the radiation-induced immune responses remain unclear. Better understanding of the mechanisms could facilitate the application of immune-activating radiotherapy and provide new treatment strategies. We previously demonstrated that tumor-specific T cell responses could be induced in esophageal cancer patients during and after chemoradiotherapy. Furthermore, in a mouse model, immune responses played an important role in determining the local and systemic therapeutic efficacy of radiotherapy that could be augmented by the immune checkpoint blockade. In this review, radiotherapy-induced immune responses, the mechanisms underlying the induction of those responses, and a practical application of the therapy are discussed.