Ado-trastuzumab emtansine (T-DM1 or Kadcyla™) is an antibody-drug conjugate (ADC) designed to deliver the antimitotic mertansine (DM1) drug to epithelial cancer cells overexpressing the oncoprotein human epidermal growth factor receptor 2 (HER2). T-DM1 has been approved in many countries for HER2-positive metastatic breast cancer (MBC) patients and has recently entered a Phase III clinical trial for advanced HER2-positive gastric cancer patients. The success of T-DM1 lies in the optimization of drug delivery to the targeted cells by the antibody while the non-reducible thioether bonds holding DM1 molecules to the antibody increase tolerability by preventing systemic release of DM1 molecules. When internalized by the targeted cell, DM1 molecules are activated and bind to tubulins, thereby inhibiting cell proliferation. Cytotoxicity of T-DM1 also arises upon binding of trastuzumab to HER2 by promoting antibody-dependent cell-mediated cytotoxicity and inhibiting HER2-dependent signaling pathways.