INTRODUCTION: Men with advanced prostate cancer now have many treatment options which include first and second-line hormonal therapy, chemotherapy, radiation therapy, (either directed external beam or systemic radio-istotope), and investigational agents on protocols. Additional adjunctive therapy with the bisphosphonate, zoledronic acid, to reduce skeletal complications should be considered. DISCUSSION: This review will discuss appropriate timing of many of these options and summarize the randomized trials demonstrating survival benefit for docetaxel and decreased skeletal morbidity for zoledronic acid. CONCLUSION: The clinical trials conducted to date do not address the question of when to give chemotherapy in the course of hormone refractory disease and the role of chemotherapy earlier in advanced disease remains to be defined. For the present, clinicians must consider many factors in determining what treatment is appropriate for the individual patient with advanced prostate cancer.