The results of this assessment of the literature indicated that neoadjuvant therapy followed by prostatectomy may improve long-term outcomes for patients with high-risk localized disease. In addition, this approach provides a paradigm for evaluating the activity and mechanism of action of new agents as correlative studies are facilitated by the availability of tumor tissue before and after therapy. The authors determined that a multidisciplinary approach involving oncologists, urologists, and pathologists is critical to the success of this model. Recent and ongoing studies of neoadjuvant therapy followed by prostatectomy were reviewed.