Adjuvant whole breast irradiation was established within the standard of care for breast-conserving therapy in the early 1980s, following the results of major randomized trials comparing mastectomy vs breast-conserving surgery and radiation. Since that time, techniques and treatment strategies have evolved, but one major thread that carries forward is the need to balance cost, efficacy, complications, and convenience. Fortunately, data from randomized trials conducted in Canada and Great Britain provide a solid framework for the consideration of hypofractionated radiation in the treatment of breast cancer. In this review we discuss the rationale and underlying radiobiologic concepts for hypofractionation, and review the clinical trials and American Society for Radiation Oncology (ASTRO) guidelines supporting this approach. We also review the practical considerations for treatment planning, including dosimetric criteria and how to approach treatment of the node-positive patient. In the current era of health-care reform and cost awareness, thoughtful utilization of hypofractionation may offer considerable savings to individual patients and the healthcare system-without compromising clinical outcomes or quality of life.