For women who opt for mastectomy as primary surgery in breast cancer, indications for adjuvant radiotherapy are also being redefined in light of evidence demonstrating that postmastectomy radiotherapy (PMRT), when given in conjunction with systemic therapy, improves, not only locoregional control, but also survival. However, in certain settings, particularly in patients wih intermediate-risk disease, and in some patients treated with neoadjuvant chemotherapy, the role of PMRT remains controversial. Here, the authors review modern data pertaining to the benefits and risks of PMRT and discuss controversies related to the indications for PMRT, focusing on patients with T1-2 breast cancer with 0-3 positive nodes and patients treated with neoadjuvant chemotherapy. They also summarize key issues related to the integration of PMRT with other treatment modalities.