Trastuzumab is the first of the monoclonal antibodies to be used in the treatment of those patients who have HER2-positive metastatic breast cancer. It is most effective when combined with cytotoxics, such as the taxanes and vinorelbine. It is well-tolerated but associated cardiotoxicity makes use with anthracyclines and in patients with cardiac dysfunction problematic. A further adverse observation is that the rate of development of cerebral metastases is 2.8-times higher in patients who have received trastuzumab as part of their treatment regimens. Trastuzumab has been combined with cytotoxics, hormones, other monoclonal antibodies, such a pertuzumab and bevacizumab, and targeted small molecules such as lapatinib, and it can be conjugated with cytotoxics to deliver them to cancer cells. The dosage, duration of therapy and optimal combinations in advanced and early stage breast cancer and use after relapse are still being defined.