HER2 positive breast cancers are characterized by their aggressive course of disease. Treatment with trastuzumab has significantly improved survival of patients with these cancers. Trastuzumab has few side effects, although in 10-15% of cases it is necessary to interrupt therapy because of cardiotoxicity, in most cases temporarily. It has become clear that patients receiving trastuzumab more frequently develop brain metastases than patients with a HER2 negative tumor. It is important to realize that patients with brain metastases from a HER2 positive breast tumor have a more favorable prognosis than patients with brain metastases from a HER2 negative tumor. Continuation of treatment with trastuzumab should be considered, next to the surgical intervention and/ or radiotherapy. Recently, lapatinib, a tyrosine kinase inhibitor, was registered by EMEA for patients with a HER2 positive tumor after previous treatment with anthracyclines, taxanes and trastuzumab. In combination with capacitabine, this agent leads to partial responses of cerebral metastases. More HER2 targeting drugs are expected to be introduced.