Trastuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER-2) protein, the mediator of an aggressive breast cancer phenotype. Trastuzumab has an important role in the treatment of metastatic breast cancer (MBC) where it improves multiple endpoints, including overall survival. More recently, striking activity is also seen in non-MBC, with substantial benefits seen in both the neoadjuvant and adjuvant settings. Experimental data has identified synergistic therapeutic effects of platinum containing chemotherapeutic regimens when combined with trastuzumab. We review the pre-clinical and rapidly evolving clinical evidence supporting platinum and trastuzumab combinations for HER-2-positive breast cancer.