Recent studies have demonstrated a survival benefit for chemotherapy in metastatic hormone-resistant prostate cancer. In other malignancies such as breast or colorectal cancer, use of active chemotherapy regimens earlier in the course of the disease has resulted in improvements in disease-free and overall survival. This review discusses the status of chemotherapy in prostate cancer and addresses evidence regarding the use of chemotherapy in hormone-sensitive disease, alone and in combination with androgen deprivation therapy.