Abstract: The widespread use of trastuzumab in recent years has led to a significant improvement in the survival of breast cancer patients with overexpressed human epidermal growth factor receptor-2(HER2-positive). However with improved systemic control and prolonged survival, the incidence of brain metastasis has increased. Brain metastasis, often in the setting of well-controlled extracranial disease, is proved to be an increasingly important and clinically challenging cause of morbidity and mortality in HER2-positive breast cancer patients. In this review, we will discuss the targeted therapies of HER2-positive brain metastasis and summarize information about ongoing clinical trials of novel therapies as well as emerging strategies for early detection and prevention.