Over the years, most innovations in hypofractionated radiotherapy for malignancies of the genitourinary tract have involved treatment of prostate cancer, which will therefore be the main focus of this chapter. The rationale for hypofractionated radiotherapy, contemporary treatment techniques, and results of clinical trials of hypofractionated external beam radiation therapy (EBRT) or stereotactic body radiation therapy (SBRT) are discussed. Finally, the implications of clinical data on general practice and future directions of research are discussed.