The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplified in 20%-30% of human breast tumors and is a marker for a poor prognosis. For these reasons, HER2 has been selected as a therapeutic target for breast cancer treatment. Oncologists can no longer ignore the importance of HER2 status for treatment algorithms in breast cancer. In light of the consequences of HER2 status on treatment selection, further research is warranted to refine and standardize HER2 testing in order to minimize false-negative results and optimize selection of treatment pathways. The anti-HER2 monoclonal antibody (MAb) trastuzumab (Herceptin) has proven valuable in treating HER2-positive, advanced-disease patients. and the availability of this novel biologic agent has important implications for clinical practice. This review describes a set of guidelines based on the current options for treatment of breast cancer. Two important factors have been taken into account in compiling these recommendations: (1) the lack of level I evidence to convincingly demonstrate the value of HER2 as a predictive marker for resistance or sensitivity to chemo- and hormonal therapy, and (2) the recently published pivotal phase II and III trial data proving the efficacy of trastuzumab as a single agent and in combination with chemotherapy in HER2-positive metastatic breast cancer.