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Metastatic breast cancer (MBC) is usually not curable, and the primary goals of treatment are thus to control disease and symptoms, maintain quality of life, and prolong life while minimizing toxicity. Chemotherapy is still an important treatment option in MBC, and the decision whether polychemotherapy is preferable to sequential monochemotherapy is under debate. Data are quite consistent in that response rates and time to progression are significantly increased with combination chemotherapy compared to the use of a single agent in MBC patients. Data regarding overall survival with polychemotherapy are not conclusive; however, frequently this approach was associated with increased treatment toxicity and decreased quality of life. Nonetheless, in patients with symptomatic or acute, life-threatening disease, where maximum and quick tumor remission is important, polychemotherapy should be the preferred approach. Furthermore, since some of the newer combination regimens seem to increase toxicity only slightly and substantially prolong time to progression, this approach may also be an option in patients without symptomatic disease.