The optimal treatment strategy for patients with high-risk localized prostate cancer remains unknown. Definitive local treatments such as radical prostatectomy and external beam radiotherapy cure only a minority of these patients. Recent efforts have been made to reduce the risk of recurrence and delay progression to symptomatic hormone-refractory disease by using chemotherapy before, during, or after definitive local therapy. Chemotherapy is an effective modality in the treatment of hormone-refractory prostate cancer. Studies have established its role in the palliation of symptoms in patients with hormone-refractory disease, though a survival benefit remains to be demonstrated. Prospective randomized trials are underway to test the hypothesis that neoadjuvant and adjuvant chemotherapy may improve survival rate in patients with high-risk localized prostate cancer. The data currently available from nonrandomized trials have not yet established the exact role of neoadjuvant and adjuvant chemotherapy and its potential impact on survival. However, preliminary data suggest that chemotherapy, when administered in concert with definitive local therapy, may be promising in patients with locally advanced prostate cancer. Randomized clinical trials are ongoing to see if neoadjuvant and adjuvant chemotherapy will translate into an improved clinical benefit for the patient, and participation by patients is paramount. We review the recent literature regarding the use of neoadjuvant and adjuvant chemotherapy in patients with locally advanced prostate cancer.