Women diagnosed with breast cancer typically undergo a multimodal approach to treating their disease. The treatments used often result in sequelae such as fatigue, hair loss, nausea and vomiting, and functional impairment. Many of these sequelae can be controlled or eliminated with pharmacological, physical, or social interventions. However, 2 effective cytotoxic agents, doxorubicin and trastuzumab, are associated with a potentially life-threatening sequela, cardiotoxicity. Currently, these agents are dosage and duration limited to circumvent cardiac damage. Exercise prior to and during the administration of these agents is emerging as a possible cardioprotective intervention based on the findings of animal model studies. Incorporating exercise into the breast cancer treatment trajectory may eliminate the dosage and duration restrictions of these antineoplastic agents and ultimately affect survival and quality of life. The authors present the pharmacological mechanism for each agent and the exciting results of animal model studies that lay the groundwork for future clinical trials.