Trastuzumab is regarded as the foundation of care for HER2-positive breast cancer as it has revolutionized the treatment of this disease across all settings. Although generally well tolerated, patients may develop symptomatic or asymptomatic cardiotoxicity, forcing a discontinuation of treatment, therefore preventing patients from benefiting from maximal disease control. Evolving research supports that trastuzumab-induced cardiotoxicity may be prevented or at least minimized by a number of prophylactic measures, such as identification of patients at risk and close monitoring. Optimized chemotherapy regimens, scheduling and formulations also contribute to minimizing cardiac adverse events. Equally important, if cardiotoxicity develops, medical interventions are now available that facilitate the reintroduction of trastuzumab once normal cardiac function has been restored. Awareness of this still-evolving information may lead to optimal use of trastuzumab, especially in combination regimens, maximizing antitumor benefit, while minimizing risk.