During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2(HER-2) positive breast cancer. Trastuzumab, pertuzumab, adotrastuzumab emtansine and lapatinib are currently food and drug administration(FDA)-approved for the treatment of breast cancer patients with HER-2 overexpressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated informationrelated to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available. Trastuzumab, pertuzumab, adotrastuzumab emtansine and lapatinib are currently food and drug administration (FDA). During the last 15 years we have witnessed an unprecedented expansion in the drug developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. -approved for the treatment of breast cancer patients with HER-2 overexpressed. However, given the amount of information gathered from the years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learned over over last years and help We will summarize the most relevant and updated informationrelated to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will critically appraise that literature in order to highlight some key clinical concep ts that should not be overlooked. lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.