The causal link between local control and long-term survival in breast cancer has become clearer over the past few years. Although the prevalence of breast cancer is high, there has been a steady decline in breast cancer mortality since the early 1990s. Improvements in breast cancer-specific mortality are the result of greater emphasis on cancer screening and improved treatment modalities, principally the development of effective adjuvant systemic therapy. Adjuvant radiation therapy (RT) substantially reduces local recurrence rates, and this reduction is even greater when combined with systemic therapy. Randomized controlled trials and meta-analyses have shown that reducing local recurrence improves overall long-term survival following both mastectomy and breast-conserving therapy. Clinical and translational research has begun to shed light on new prognostic and predictive markers that can assist in the assessment of an individual patient's risk of local recurrence without RT and the likelihood of a survival benefit with RT. The ability to appropriately tailor therapy to reduce local recurrence rates is vital toward continuing the decline in breast cancer mortality.