The clinical management of cancer is being revolutionized by agents that activate the immune system against the tumor. Nevertheless, many of these therapies benefit only to a minority of patients. In this context, radiotherapy is holding great promises as a means to complement immunotherapy in the management of malignant disorders. In particular, radiotherapy can generate an “in situ vaccination” effect that is at the foundation of optimal immune responses against cancer cells. Thus, the clinical potential of combining immunotherapy with radiotherapy is extraordinary.