BACKGROUND: An expanded understanding of the biology of breast cancer has led to the identification of the HER-2 receptor as an important growth factor. This receptor possesses intrinsic tyrosine kinase activity and has been associated with aggressive biological behavior and poor clinical outcome. METHODS: Data have been reviewed regarding the role of HER-2 expression as a prognostic variable, as a predictive factor for response to chemotherapy and hormonal therapies, and as a directed therapeutic target for breast cancer. RESULTS: Therapy with a humanized monoclonal antibody to HER-2 (trastuzumab) can be effective treatment in some patients with metastatic breast cancer, either given alone or in combination with some chemotherapeutic agents. Cardiac toxicity limits concurrent use with anthracyclines. Clinical trials will further define optimal combination regimens with this agent, and its value in patients with localized or locally advanced stages. CONCLUSIONS: Trastuzumab is a significant addition to the armamentarium against breast cancer. Standardization of the optimal method to evaluate for HER-2 overexpression is necessary to better define its role as a prognostic, predictor, and therapeutic target in this disease.