The hypofractionation of stereotactic body radiotherapy (SBRT) for prostate cancer has become a broad topic, and there are many aspects to consider before accepting this treatment into our clinics. Among the considerations are the data from the Stanford phase II trial, a seminal investigation into this area, which will be presented and reviewed here. A single-arm, prospective phase II trial was initiated at Stanford in December of 2003. This trial uses SBRT as monotherapy for 'low-risk' prostate cancer patients, and 69 patients have been entered to date. We have analyzed the patient data for the first 5 years of this study. For study entry, patients were required to have clinical stage T1c or T2a disease, prostate-specific antigen (PSA) ≤ 10 and a Gleason score of 3 + 3 (or 3 + 4 if the higher grade portion was of small volume, usually <25% of the cores involved). No prior treatment was permitted, including the use of transurethral resections or androgen deprivation therapies. A low urinary IPSS score of < 20 was required for study entry as well. The prescription dose was 7.25 Gy for 5 fractions for a total dose of 36.25 Gy. This was normalized to cover ≥ 95% of the planning target volume with 100% of the prescription dose. Patients were treated using CyberKnife technology. To date, excellent PSA responses have been observed in patients with lower-risk disease selected for treatment and receiving 36.25 Gy in 5 fractions. To date, sexual quality of life outcomes have also been approximately comparable to other radiotherapy approaches. Rates of late GI and GU toxicity have been relatively low and generally comparable to dose-escalated approaches using conventional fractionation.