In the United States, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men. Prostate cancer is a rare disease before age 40; however, the prevalence increases quickly to 80% by the age of 80, and with increasing life expectancy, hormone-refractory prostate cancer (HRPC) will soon represent the most common cancer in the male population in the United States and other Western countries. The evolution of early prostate cancer is variable and extends over many years; some tumors progress slowly or not at all, whereas others may progress more rapidly and be fatal after a few years. A widely held view is that chemotherapy has no role in HRPC because no single agent or combination has been shown to prolong survival in a randomized trial. This concept may be obsolete, as preliminary results for a number of approaches, mostly derived from laboratory observations, show that prostate cancers are not as resistant to chemotherapy as traditionally believed. The population of early "geriatric" HRPC patients is rapidly increasing, posing an even greater challenge to oncologists in coping with this difficult-to-manage patient population. In this article, we analyze the most novel chemotherapeutic combinations for the treatment of HRPC in otherwise healthy elderly men.