Prostate cancer is a significant health concern for men worldwide. It continues to be the most common lethal malignancy diagnosed in American men and the second leading cause of male cancer mortality. Hormone-refractory prostate cancer (HRPC) remains clinically challenging. Two large phase III studies have demonstrated a survival advantage in HRPC patients utilizing docetaxel chemotherapy, setting a new standard of care for this disease. This paper examines the progress that has been made in HRPC with the Taxanes (Docetaxel, Paclitaxel, and Epothilones) with a glimpse on mechanisms of resistance and on combinations able to overcome it. In addition, new targeted therapies under development in combination with taxanes are reviewed with an explanation of their molecular mechanisms of action.