Neratinib is a potent, irreversible, small molecule panErbB inhibitor of EGFR, HER2 and HER4 tyrosine kinases. Its activity prevents the autophosphorylation of HER2 and thus halts the downstream activation of this key proliferative pathway in tumors dependent on HER2 overexpression or EGFR activation. It has shown promising clinical activity in women with HER2+ stage 2 and 3 breast cancer in the neoadjuvant setting (I-SPY 2 TRIAL) and in women with stage 4 metastatic breast cancer, although evaluation in larger phase 3 trials is required to confirm these results.