Trastuzumab emtansine is a unique antibody-drug conjugate targeting selectively human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells, thus conferring high efficacy with minimal systemic toxicities. Trastuzumab emtansine consists of a monoclonal antibody trastuzumab and potent cytotoxic agent DM1, combined together through a stable thioether bond. First-in-man phase I study set the maximum tolerated dose at 3.6 mg/kg given intravenously on a 3-weekly regimen. In phase II studies, trastuzumab emtansine at 3.6 mg/kg provided objective tumour responses and clinical benefit with an encouraging safety profile. Over these studies, trastuzumab emtansine had favourable pharmacokinetics. No accumulation of trastuzumab emtansine or catabolites was observed even after repeated dosing and free DM1 was very low in circulation. The stability of trastuzumab emtansine in circulation justifies the minimal systemic toxicity observed. Recently, a randomised international open-label phase III study confirmed the efficacy and safety of trastuzumab emtansine versus lapatinib plus capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer. Overall survival was significantly improved in the trastuzumab emtansine arm. Safety outcomes were also favourable. The adverse events traditionally related to chemotherapy were markedly lower or absent with trastuzumab emtansine. Cardiotoxicity, frequently observed in HER2-directed therapy, was not reported. Although thrombocytopenia and elevations in hepatic enzymes were reported with trastuzumab emtansine, these events were reversible and manageable. Ongoing trials investigating trastuzumab emtansine as a single-agent or in combination with other agents, will determine the place of trastuzumab emtansine in the current therapeutic strategies deployed for HER2-metastatic breast cancer.