Trastuzumab (Herceptin) is a therapeutic monoclonal antibody specific for the human epidermal growth factor receptor type 2 (HER2), a cell-surface tyrosine kinase receptor overexpressed by 25% to 30% of breast cancers. The drug is now regarded as one option for standard therapy in HER2-overexpressing metastatic breast cancers. It is associated with a moderate response rate as a single agent, and in combination with standard chemotherapy, can produce greater response rates and prolong the survival of women with advanced breast cancer. Its activity in metastatic breast cancer has led to active clinical trials examining its potential role in the neoadjuvant and adjuvant settings. The successful clinical development of trastuzumab provides further proof of principle that biologically targeted therapies can have a profound impact on the management of breast cancer. Here we review the clinical development of this novel agent, emphasizing the potential for therapeutic synergy when trastuzumab is combined with both standard chemotherapy and innovative molecularly targeted and biologic agents.