The development of adjuvant therapy has made a significant positive impact on clinical outcomes for patients with breast cancer. Over the past 30 years the field of adjuvant therapy has evolved from its cyclophosphamide/methotrexate/5-fluorouracil beginnings by adding new agents and modifying treatment schedules and dosing. More recently, the application of targeted therapies based on hormone receptor status and HER2 expression is providing a new level of efficacy for these patients. The biologic agent trastuzumab, a monoclonal antibody directed against HER2, first demonstrated significant activity in patients with metastatic breast cancer, reducing the risk of death by 30%. The agent was then evaluated in an adjuvant setting in several large trials. In a recently published joint efficacy analysis, the addition of trastuzumab to standard adjuvant chemotherapy regimens led to a 52% reduction in events (ie, recurrent cancer, second primary cancer, or death before recurrence) and a significant improvement in overall survival. These dramatic findings highlight the need for accurate HER2 testing to best identify the HER2(+) patients who would benefit from the treatment. Currently there is some debate about how to best approach HER2 testing: with the protein-based immunohistochemistry or the genetic-based fluorescence in situ hybridization. Current research evaluating the different techniques may help to settle this question. Finally, new targeted agents are being investigated and ongoing research aims to identify additional potential therapeutic targets to further improve outcomes for these patients.