Docetaxel based chemotherapy has been shown to modestly extend life, relieve pain and improve the quality of life in patients with metastatic castration-resistant prostate cancer. Current trials are attempting to build on the backbone of docetaxel by combining it with novel biological agents. Trials are also investigating the role of docetaxel for earlier stages of prostate cancer. No standard second-line systemic therapy exists and such patients are candidates for clinical trials. The increased understanding of the mechanisms of progressive castration-resistant prostate cancer is being translated into an increasing pipeline of novel therapies.