Breast cancer is the most common cause of cancer among women in the United States, with approximately 260,000 new cases of breast cancer and more than 40,000 breast cancer related deaths anticipated in 2018. Fortunately, an improved understanding of the importance of tumor biology has led to significant advances in the management of breast cancer in both the adjuvant and metastatic settings, as well as an improvement in patient morbidity and breast cancer specific survival. When an abnormality is detected on screening, breast cancer diagnosis and management typically require a multidisciplinary approach that incorporates some combination of radiology, surgery, pathology, medical oncology, radiation oncology, and/or specialists in rehabilitation. This chapter provides an overview of the principles of using systemic therapy (i.e., medications that are absorbed and carried throughout the bloodstream, such as chemotherapy and endocrine therapy) for the management of breast cancer.