Personalized medicine is emerging as an important guiding principle in diagnosis and treatment. This means not just doing more for some, but safely doing less for others. The lessons learned about the biology of breast cancer over the last 2 decades have enabled us to understand the incredible heterogeneity of breast cancer and its associated behavior. Although much work remains, there is an emerging opportunity to identify and recognize more indolent forms of breast cancer, made more prevalent through the widespread adoption of screening. With our improving systemic therapies and improved molecular tools, we now have the opportunity to reduce the burden of treatment in women with lower-risk tumors. Our surgical treatments have evolved, with less morbid and more cosmetic procedures. In this article, we review the indications for further reducing local therapy, including adjuvant radiation.