Despite progressive developments in therapeutic interventions, including surgery, radiotherapy and chemotherapy, there has been no major improvement in the survival of women with metastatic breast cancer (MBC). Based on knowledge of tumor growth patterns, approaches addressing this issue have included increasing chemotherapy dose or dose density and extending the duration of therapy. However, only the latter approach has resulted in improved clinical benefit, although not survival; and its use is restricted by the cumulative toxicity of chemotherapeutic agents. Therefore, the best hope for improved survival lies with new classes of anticancer drug and particularly biological agents. This review focuses on the first oncogene-targeted therapy for human epidermal growth factor receptor-2 (HER2)+ MBC patients. The humanized anti-HER2 monoclonal antibody Herceptin has proven clinical benefits in HER2+ MBC patients, most importantly improved survival, and is rapidly becoming a standard of care for these patients. In contrast to the fixed number of cycles used for chemotherapeutic agents, Herceptin is administered until disease progression, with some data suggesting that continuation beyond disease progression should be investigated. The preclinical and clinical findings on which the current recommended duration of Herceptin therapy are based are reviewed and alternative strategies are discussed.