This is the reason why the interest for combined radiotherapy and immunotherapy approaches focusing on the abrogation of Treg suppression has increased in cancer therapy in the last few years. Here we summarize the basic mechanisms of Treg radiation response both in healthy and cancerous environments and discuss Treg-targeted pre-clinical and clinical immunotherapy approaches used in combination with radiotherapy. Finally, the discrepant findings regarding the predictive value of Tregs in therapy response are also reviewed.