Docetaxel (Taxotere®) is a well established anti-mitotic chemotherapy agent. Among other therapeutic indications, docetaxel plus prednisone is indicated for first-line chemotherapy in patients with castration-resistant prostate cancer (CRPC). Docetaxel every 3 weeks plus continuous prednisone has been standard first-line chemotherapy in CRPC since demonstrating improved survival compared with the previous standard regimen, mitoxantrone plus prednisone, in the phase III TAX 327 trial in 2004. Since that time, docetaxel has been combined with various agents that demonstrated additive or synergistic activity in preclinical studies in an effort to further improve outcomes, but to date, overall survival has not been extended compared with docetaxel plus prednisone. However, several promising agents are emerging with a potential role in docetaxel-based combinations based on efficacy and manageable toxicity, including bevacizumab, dasatinib and atrasentan. In the TAX 327 trial, neutropenia was relatively common in the group receiving 3-weekly docetaxel plus prednisone, but infection was rare. The tolerability of a weekly docetaxel regimen also administered in this trial was not significantly different to that of the 3-weekly regimen, except for a lower incidence of grade 3 or 4 neutropenia. However, weekly or 2-weekly docetaxel administration schedules may have a place in very elderly or frail patients in order to improve tolerability compared with the 3-weekly regimen. In conclusion, docetaxel every 3 weeks plus prednisone remains the optimum first-line chemotherapy for most patients with advanced CRPC until such time that ongoing research with docetaxel and emerging therapeutic agents can demonstrate improved survival.