The indications and benefits of postmastectomy radiation therapy (PMRT) continue to evolve. Advances in systemic adjuvant therapy and targeted therapy for breast cancer are likely to play an increasingly important role in control of locoregional as well as distant disease. Ongoing scrutiny of patterns of chest wall failure will be required to define the net benefit derived from PMRT. This article discusses the 2001 American Society of Clinical Oncology guidelines for PMRT and current practices using PMRT in selected groups of patients who have breast cancer.