Simple SummaryWhile surgery remains the main treatment modality for non-melanoma skin cancer (NMSC), radiotherapy still plays a major role in the treatment algorithm, even with the emergence of immunotherapy and the revolution it is causing in treatment paradigms. The aim of our review is to describe the role of radiotherapy in the definitive and adjuvant setting for NMSC. We also aim to describe the role of radiotherapy combined with immunotherapy in these cases.AbstractNon-melanoma skin cancer (NMSC) is the most common malignancy in the United States. While surgery is considered as the main treatment modality for both cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC), radiotherapy plays an important role in the treatment of NMSC, both in the adjuvant setting for cases considered high-risk for recurrence, and in the definitive setting, when surgery is not feasible or desired by the patient. The last years have seen the emergence of immunotherapy treatment for cases of advanced cSCC in the palliative, and possibly neoadjuvant settings, making the treatment paradigm more complex. In this review, we attempt to describe the different radiation modalities available for the treatment of NMSC, the indications for adjuvant post-operative treatment with radiotherapy for cSCC, the role of radiotherapy in elective neck treatment, and the efficacy, safety, and toxicity profile of this treatment in these different settings. Furthermore, we aim to describe the efficacy of radiotherapy combined with immunotherapy as a promising horizon for treating advanced cSCC. We also aim to describe the ongoing clinical studies that attempt to examine future directions for the role of radiation treatment in NMSC.