Across radiation oncology disciplines, from breast cancer to prostate cancer, the last decade has seen a trend toward shorter courses of definitive radiotherapy, termed hypofractionation. The main driver of this trend is the availability of better imaging, planning, and radiotherapy technology, which allows significantly more precise treatment delivery. Thus, the radiation dose delivered to nontarget tissues has declined dramatically, allowing many radiation oncologists to feel comfortable delivering higher daily doses, resulting in shorter treatment courses. Furthermore, the success of stereotactic body radiotherapy has raised the question of whether our understanding of radiation biology has underappreciated the effects of higher doses per fraction on tumor control.