Over the past several years, the clinical presentation of prostate cancer has evolved so that more patients than ever before are presenting with clinically localized disease. However, a significant number of men continue to present with locally advanced or metastatic prostate cancer, or go on to develop metastasis after failing local therapies. Despite our better understanding of the biological principles and newer therapies, metastatic prostate cancer remains a lethal disease. Androgen ablation continues to be the first, most effective line of treatment for advanced/metastatic prostate cancer. Newer chemotherapy combinations with increasing activity are being identified in hormone-resistant prostate cancer. Based on novel targets, new treatment strategies are being developed and incorporated into clinical trials. Ultimately, the impact of these evolving treatments on advanced/hormone-resistant prostate cancer can best be assessed by well-designed phase III trials, many of which are now being launched or awaiting completion.