Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men and continues to be a major cause of morbidity and mortality. Death from prostate cancer is associated with objective and biochemical progression following hormonal manipulations often described as hormone refractory prostate cancer (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has to be balanced against potential treatment-related side effects. Therapeutic efficacy may be assessed by evaluating the percentage of patients obtaining a PSA decline of > 50%, evaluating the response of bidimensionally measurable disease or by improvements in quality of life assessments. The most effective cytotoxic therapies at the present time seem to be combinations of estramustine phosphate with taxanes and etoposide. Regimes employing ketoconazole with estramustine, vinblastine or bisphosphonates seem to be worthy of further evaluation. Mitoxantrone has an impressive palliative effect in patients, particularly when combined with hydrocortisone. Oral chemotherapeutic regimens with a combination of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less toxic alternative. For the future we need prospective randomized clinical phase-III studies, prognosticators identifying patients as being at high or low risk who might benefit from different therapeutic approaches and generally binding eligibility and response guidelines in order to be able to compare trials of different therapeutic approaches.