Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin’s lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.