Approximately 15%-20% of breast cancer is HER2 positive, and patients with this subtype of disease historically had worse outcomes than patients with HER2-negative disease. However, the introduction of HER2-directed therapies has dramatically altered outcomes for these patients, especially for persons with early disease. However, despite these achievements, metastatic disease is still not curable. This review summarizes the current treatment approach for patients in the preoperative and adjuvant setting, including data regarding selecting the optimal chemotherapy partner as well as determining the duration and type of anti-HER-directed therapy. This article also reviews how to approach patients with advanced HER2-positive disease and discusses promising new therapies that are in development.