Attempts to carry out clinical trials to improve the treatment of breast cancers, including chemotherapy and targeted oncologic therapies, often exclude women with baseline cardiovascular compromise, such as low ejection fraction or arrhythmia. Therefore, despite concrete evidence of cardiotoxicity from a select number of chemotherapeutic agents, it has been difficult to better characterize the progression of cardiac dysfunction in women with preexisting cardiac conditions who receive chemotherapy. Women who have impaired cardiac function should be included in future clinical trials, or at least placed in separate trials with careful monitoring, to better assess this high-risk population. This article will discuss the epidemiology, mechanisms, diagnostic methods, and management of cardiotoxicity from systemic chemotherapy used to treat breast cancer.