Over 60 years ago, Huggins and Hodges discovered androgen deprivation as an effective first-line therapy for metastatic prostate cancer. This leads to significant cancer control but in almost all men prostate cancer ultimately progresses to a hormone-refractory (HRPC) state resulting in significant morbidity and eventual death. In 2004, two landmark studies using docetaxel based chemotherapy demonstrated, for the first time, a survival advantage in HRPC. This has set a new standard of care for this disease. In addition, treatment with the bisphosphonate zoledronic acid has been shown to significantly reduce bone complications in metastatic HRPC. Building on these advances, several new docetaxel/zoledronic acid based combinations as well as new targeted therapies are under development. Introducing these effective therapies earlier in high risk patients is also under investigation to further improve outcomes.