Radiotherapy can increase the cell cycle arrest that promotes apoptosis, reduces the risk of tumor recurrence and has become an irreplaceable component of systematic treatment for patients with breast cancer. Substantial advances in precise radiotherapy unequivocally indicate that the benefits of radiotherapy vary depending on intrinsic subtypes of the disease; luminal A breast cancer has the highest benefit whereas human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) are affected to a lesser extent irrespective of the selection of radiotherapy strategies, such as conventional whole-breast irradiation (CWBI), accelerated partial-breast irradiation (APBI), and hypofractionated whole-breast irradiation (HWBI). The benefit disparity correlates with the differential invasiveness, malignance, and radiosensitivity of the subtypes. A combination of a number of molecular mechanisms leads to the strong radioresistant profile of HER2-positive breast cancer, and sensitization to irradiation can be induced by multiple drugs or compounds in luminal disease and TNBC. In this review, we aimed to summarize the prognostic differences between various subtypes of breast tumors after CWBI, APBI, and HWBI, the potential reasons for drug-enhanced radiosensitivity in luminal breast tumors and TNBC, and the robust radioresistance of HER2-positive cancer.