Many women undergo mastectomy as treatment of their breast cancer either because of personal preference or because of tumor-related factors making mastectomy the preferred surgical option. The use of postmastectomy radiation therapy has been shown to decrease the risk of local recurrence and in some cases improve overall survival. Decisions regarding the need for postmastectomy radiation therapy can be complex and rely on careful review of many factors. Lymph node status, tumor size, tumor grade, receptor status, presence or absence of lymphovascular space invasion, Her-2/neu status, margin width, and patient age all need to be considered when making recommendations for or against postmastectomy radiation therapy. In this article, we provide a review of the relevant literature pertaining to postmastectomy radiation therapy in order to help guide this decision-making process.