Locally advanced prostate cancer generally refers to those patients with clinical stages T3-4 disease. Patients with locally advanced cancer frequently are included in clinical trials that examine treatment for patients at high risk for relapse based on presenting prostate-specific antigen, high Gleason score, or advanced clinical stage. There is a growing body of evidence that suggests that men with localized prostate cancer benefit from high-dose radiation therapy delivered with three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, or proton beam therapy. Most importantly, neoadjuvant and adjuvant androgen-deprivation therapy have significantly improved outcomes in men with locally advanced or high-risk prostate cancer. Although questions remain regarding the optimal timing and duration of adjuvant hormonal therapy, a combination of long-term androgen deprivation started before radiation therapy and continued for 2 years represents a North American standard of care for this patient population.