With estramustine phosphate the clinician has the possibility to ensure complete hormonal as well as cytotoxic control of advanced prostate cancer with a single drug. EMP is considered as a first choice for treatment of hormone refractory prostate cancer. It is at least as effective as conventional chemotherapy, yet less aggressive with regard to its toxicity profile. EMP is particularly useful in patients with limited bone marrow reserve, e.g. in case of prior or associated radiotherapy. As to the use of EMP in primary treatment, more information is required before we can define with certainty subgroups of patients who would benefit more from an early course of EMP than from other hormonal therapy. The existing data point in the direction of poorly differentiated tumors, patients with bone pain and poor prognosis. EMP treatment is associated with an increased risk of cardiovascular morbidity. This should be avoided as much as possible by proper selection of patients or by prophylaxis. Gastro-intestinal side effects, such as nausea, diarrhea and anorexia are dose-dependent. These adverse events tend to interfere with compliance at dosages over 560 mg/day. Dosage modifications or an anti-emetic may help. The intravenous administration of EMP offers the possibility for high loading doses at a substantially reduced risk for cardiovascular and gastrointestinal side effects.