We have evaluated the role of chemotherapy for the treatment of prostate carcinoma. The data of patients with endocrine-resistant stage D2 disease indicate that clinical benefits in such patients are at best marginal. Despite the controversies involved in the assessment of response in this disease, in this review we show that in over 3,000 patients eligible for evaluation, less than 10% had complete or partial responses to various treatment regimens. Survival evaluation on all prospective randomized clinical trials showed no advantages in favor of any treatment tested and, moreover, in 2 of such studies involving various single agents, survival was not better than a "no chemotherapy" control arm. Because of these data, we conclude that chemotherapy is not indicated as an adjuvant treatment for patients with localized prostate cancer. Although patients with prostate cancer frequently respond to androgen deprivation procedures, preclinical and clinical data strongly suggest the existence of endocrine-independent cell clones, which supports further testing with nonhormonal cytotoxic treatment. A close multidisciplinary interaction is a prerequisite for development of new effective systemic treatment in this disease.