Prostate cancer is the second most common cause of cancer death in American men and represents a significant factor in US health care costs. Radiation therapy serves as one of the most effective treatments for prostate cancer. However, radiation is also an expensive treatment modality and is a significant contributor to the overall rise in the cost of prostate cancer care. Currently, standard external beam radiation therapy for prostate cancer consists of between 75.6 and 81.0 Gy of radiation separated into 1.8- to 2-Gy doses (or "fractions") given daily for between 7 and 9 weeks. Recently, relatively shorter treatment schedules delivering more radiation per treatment-consisting of fractions > 2 Gy-over shorter time periods have been proposed in an effort to curtail rising health care costs and improve patient convenience. However, significant uncertainty still remains regarding outcomes from this type of more condensed treatment, known as"hypofractionated"radiation. In this article, we provide the historical background and rationale for hypofractionated prostate cancer treatment, discuss the potential benefits and risks of prostate hypofractionation, and review the clinical evidence regarding the effectiveness of hypofractionated radiation therapy for prostate cancer.