Radiation therapy is a cornerstone in solid cancer management in all phases. Apart from the direct tumor cells death, in the last years, there was an increasing interest in understanding possible interactions between radiotherapy and cancer immunity. The so-called abscopal effect represents an interesting field of research to understand the possible biological and clinical mechanisms to translate in clinical practice. Although the abscopal effect is uncommon, this phenomenon has been documented in various types of cancer, including melanoma, breast, lung, and liver cancers. Moreover, new conceptions and clinical strategies have been hypothesized with the intent to ameliorate tumor response combining immunotherapy and ionizing radiation. There is growing interest to exploit the synergistic effect of adding immune checkpoint inhibitors and radiotherapy in the daily clinical practice.