Trastuzumab is the first antibody that has shown clinical activity in patients with HER-2-positive breast cancer. The mechanism of action is not fully understood; however, antibody-derived cellular cytotoxicity (ADCC) is considered to explain important peculiarities of its clinical activity such as treatment beyond progression. Based on early pre-clinical data, trastuzumab was used beyond progression since the start of its clinical use. Initially evidence to use trastuzumab beyond progression came only from observational studies, which might have been biased by the unknown decision criteria for or against continuation of trastuzumab. Only recently, the randomised GBG 26 study demonstrated that capecitabine and continuing trastuzumab beyond progression achieved a higher response rate and longer progression-free survival than capecitabine alone. Supportive evidence came from studies combining trastuzumab with lapatinib or pertuzumab in trastuzumab pre-treated patients, showing better results than the same treatment without trastuzumab. A blockade of HER-2 throughout all stages of Her-2-positive breast cancer should therefore be considered.