The HER2 gene is overexpressed in 15–20 % of all breast cancers. With the advent of HER2-directed therapies, HER2 overexpression is no longer considered an adverse prognostic factor. Despite significant improvements in clinical outcomes with the use of trastuzumab [herceptin (H)], women aged >65 years remain underrepresented in most clinical trials. Cardiac safety in the elderly woman is a major concern because of pre-existing comorbidities. However, many studies suggest that elderly patients with HER2-positive disease derive the same benefit from trastuzumab as do their younger counterparts in both adjuvant and metastatic settings. Data are limited guiding safety and efficacy of other HER2 inhibitors such as pertuzumab and trastuzumab emtansine in elderly patients; however, in general, these drugs have a favorable toxicity profile.