Hypofractionated radiotherapy for prostate cancer has become of increasing interest with the recognition of a potential improvement in therapeutic outcome with treatments delivered in large-sized daily fractions. In addition, hypofractionation offers a reduction in fraction number and produces attractive cost and increased convenience for patients. There is convincing evidence, by several clinical trials, that biochemical control is significantly improved with higher administered radiation doses to the prostate gland. Furthermore, the improved radiation delivery techniques such as 3D conformal radiotherapy (3DCRT) or, better, intensity modulated radiation therapy (IMRT) allow high administered doses to the prostate while sparing the normal surrounding tissues. Several studies of the radiobiology of prostate cancer suggest that it may be more susceptible to large fraction sizes compared with conventional fractionation of external beam radiation.