The medical management of hormone-refractory prostate cancer remains difficult and largely palliative. The development of effective antineoplastic agents has been frustrated by difficulty in the establishment of satisfactory objective response criteria for clinical trials. Nevertheless, recent trials indicate that mitoxantrone and spindle toxins such as docetaxel do show activity. Estramustine-based regimens have also been promising, and such combination regimens are now being explored rigorously. Benefiting from new molecular-biologic insights into the pathobiology of prostate cancer, novel strategies targeting new molecular pathways of cell regulation and cell-cell interaction (such as angiogenesis) are also being actively pursued.