Treatment with docetaxel-based chemotherapy results in improved survival in patients with metastatic castration-resistant prostate cancer. However, all patients eventually develop progressive disease associated with poor outcomes. In this article, we discuss the available second-line therapeutic options following docetaxel, with a special focus on cabazitaxel, which is the first agent to yield extended survival as second-line therapy following docetaxel. Cabazitaxel, a novel semi-synthetic taxane, is effective even in docetaxel-resistant model systems. Recently, results of the Phase III TROPIC trial demonstrated improved survival with cabazitaxel plus prednisone compared with mitoxantrone and prednisone in patients with progressive metastatic castration-resistant prostate cancer, following prior docetaxel, which led to approval by the US FDA.