In 1985, a growth factor pathway that depends on the presence of a tyrosine kinase transmembrane receptor present on the surface of 20–25% of breast cancer cells was discovered. The receptor is called human epidermal growth factor receptor (HER)-2 and the prognosis of those patients whose tumors overexpress it is poor. In the 1980s, a monoclonal antibody against this receptor, trastuzumab, was developed and, in 1998, approved for the treatment of metastatic breast cancer. In 2005, the results of five trials evaluating trastuzumab in the adjuvant setting, involving more than 10,000 women, were presented. Despite differences in design and having a short follow-up (between 1 and 2 years), these studies show the same astonishing results that adjuvant trastuzumab therapy halves the recurrence rate and reduces mortality by 30% in those trials mature enough to show survival gains. This benefit is, on average, higher than that of adjuvant chemotherapy and similar to that seen with adjuvant hormonal therapy. The main setback of trastuzumab is its potential for cardiotoxicity, although benefits seem to outweigh risks and the ensuing congestive heart failure is generally reversible. Today, the evaluation of HER-2 expression should be mandatory in every early breast cancer patient, since without it, there is the risk that access to this highly effective drug will be denied for women belonging to this unfavorable subgroup of patients.