Metastatic breast cancer is a partially chemotherapy-sensitive neoplasm. Docetaxel appears to be the most active single agent for this condition. The platinum coordination complexes are also active, but are seldom used. An emerging literature suggests that taxane-platinum combinations have substantial activity. Trastuzumab, a molecularly targeted therapy for metastatic breast cancer is active as a single agent in HER2-overexpressing disease, and has been demonstrated to augment the activity of other agents in random assignment trials. Preclinical data suggest a powerful synergistic interaction between trastuzumab and both platinum and docetaxel. In early trials, platinum-taxane-trastuzumab combinations have exhibited promising clinical activity. The potential for cardiac toxicity when trastuzumab is combined with the anthracyclines suggests a further rationale for the development of non-anthracycline regimens, especially in the adjuvant setting. Randomized, multicenter, phase III trials in the metastatic and adjuvant setting are currently underway to test the hypothesis that synergistic combinations of docetaxel, platinums, and trastuzumab will result in superior safety as well as efficacy.