Increasing use of targeted anticancer agents that inhibit tyrosine kinase signaling (monoclonal antibodies or tyrosine kinase inhibitors) has dramatically improved the survival of patients with malignancies. However, cardiotoxicity, including heart failure, left ventricular dysfunction, hypertension, myocardial infarction, and thromboembolism, has occurred. Importantly, these cardiotoxicities are at least partially reversible and responsive to medical management. Early recognition of cardiovascular side effects is vital to allow long-term, continuous therapy with these life-prolonging agents. This article reviews potential cardiovascular side effects of frequently used inhibitors of tyrosine kinase activity (eg, trastuzumab, sunitinib) and discusses the diagnosis and management of cardiotoxicity associated with targeted therapy.