Pretreatment prostate-specific antigen (PSA) level is the single most important prognostic factor for patients undergoing radiotherapy for clinically localized prostate cancer. When combined with Gleason score and T-stage, pretreatment PSA enhances our ability to accurately predict pathologic stage. Patients with pretreatment PSA levels > 10 ng/mL are at high risk for biochemical failure when treated with conventional radiation alone. A PSA nadir of > 1 ng/mL and a post-treatment PSA > 1.5 ng/mL are associated with a high risk of biochemical failure. Postoperative radiotherapy delivered while the tumor burden is low (eg, PSA < 1 ng/mL) predicts a favorable outcome. Many of these conclusions about the usefulness of pretreatment PSA are based on the assumption that PSA can be used as a surrogate end point for disease-free and overall survival from prostate cancer. However, this assumption still remains to be validated by phase III trials.