The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On 8 June 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint. Areas covered: The review provides insights into the main mechanisms of action of pertuzumab. In addition, it gives complete coverage of the landmark clinical and translational trials for this agent. Expert opinion: The new therapeutic algorithm in the treatment of HER2-positive advanced disease and the awaited results of the Aphinity trial are expected to impact the sequence of anti-HER2 treatment. Accordingly, the value of pertuzumab beyond progression needs to be properly studied. Furthermore, to improve the toxicity profile and efficacy of future treatment, new pertuzumab-based regimens are being investigated.