Despite years of clinical study, there are still many unanswered questions regarding postmastectomy radiation. It is clear that radiation therapy plays a critical role in the multidisciplinary management of patients with locally advanced or inflammatory breast cancer. It is also accepted that postmastectomy radiation is not required for most women with noninvasive disease or stage I disease. Randomized clinical trials studying radiation treatments for women with stage II or III breast cancer have shown that the addition of radiation after mastectomy can reduce local-regional recurrence rates, which then improves survival. However, other data have indicated that the risk of local-regional recurrence after mastectomy and chemotherapy is low for patients with small tumors and one to three positive lymph nodes, leading some to question whether postmastectomy radiation is useful for this group. A second controversy regards the sequencing of postmastectomy radiation and breast reconstruction. In this article we discuss these controversies, review the data that are relevant, and provide our institutional approaches to these issues.