Anthracyclines and trastuzumab are key agents in the management of patients with breast cancer, and have revolutionized the management of both early-stage and advanced-stage disease. The use of anthracyclines, however, can be compromised by the potential for cardiotoxicity; trastuzumab also has the potential for causing cardiotoxicity in patients receiving concurrent or prior anthracyclines. Although its development is treatment limiting, cardiotoxicity can be minimized with appropriate clinical care and drug scheduling. We discuss the efficacy of trastuzumab, its potential for cardiac compromise, and its interaction with anthracyclines. We highlight biological mechanisms that might be responsible for cardiotoxicity, describe the established and trial schedules of both agents, and discuss clinical strategies used to minimize the risk of developing cardiac failure through appropriate scheduling of trastuzumab with anthracyclines.