Prostate cancer is the most common cancer among American men and the second most common cause of cancer deaths among men. Treatment of prostate cancer remains a challenge. Despite decades of research, few cytotoxic chemotherapy agents have shown promise against prostate cancer. In this paper, we will discuss the history of chemotherapy in prostate cancer, the pivotal trials with docetaxel that advanced the field, the cytotoxic chemotherapy agents, including cabazitaxel, as well as combination therapy with docetaxel or cabazitaxel and the potential implications of biomarkers such as AR-V7 in chemotherapy use.