Abstract Over the last two decades, considerable progress has been achieved in the management of cancer with the introduction and use of molecular targeted therapies (MTTs). MTTs have proven particularly efficiency in the treatment of metastatic kidney, breast, colon, lung carcinoma, gastrointestinal stromal tumors (GISTs), and chronic myeloid leukemia. Nevertheless, MTTs can inhibit major pathways in normal or noncancerous cells leading to unexpected offtarget side effects, morbidity, reduced drug doses, or even drug cessation. Cardiac toxicities associated with MTT include left ventricular systolic dysfunction (LVSD), clinical overt heart failure, conduction abnormalities, QT prolongation, acute coronary syndrome, and hypertension.. The frequency of MTT-induced cardiotoxicity is largely unknown or underestimated, but appear to be variable and dependent on the agent used. One of the most threatening complications of MTT is QT prolongation with the risk of torsades de pointe and sudden death. MTT-induced cardiotoxicity was first reported with trastuzumab. Cases of heart failure have also been reported after treatment with imatinib, and adverse cardiac effects are mentioned in the prescribing information for dasatinib, sunitinib, sorafenib, and bevacizumab. However, cardiotoxicity is clearly not a ‘class effect’ of tyrosine kinase inhibitors (TKIs) because it seems to be uncommon with some TKIs, such as those targeting the epidermal growth factor receptor. Consequently, cardiotoxicity should be determined for each agent on a case-by-case basis. This review, will examine the incidence and molecular mechanisms of MTT-associated cardiovascular events Oncologists and cardiologists should remain aware of the risks for cardiovascular disease in patients receiving MTT. It is important that oncologists understand the need to adequately assess cardiac function and vascular risk because many patients with cancer are more likely to die of heart disease than cancer. Similarly, it is also necessary to alert cardiologists about the increased risk for cardiovascular events in the cancer patient population and educate them on how to deal with them. A clinical endpoint for patients with cancer, particularly those at high risk for a cardiovascular event, should be the prevention and optimal management of cardiovascular risk factors. Patients should be encouraged to follow standard guidelines for reducing cardiovascular risk. BP control, lipid level reduction, and lifestyle modifications to include exercise and smoking cessation are suggested for prevention, and early identification of cardiovascular disease should be undertaken. This approach involves the patient's primary care physician, the oncologist, and the cardiologist. The goals of the multidisciplinary management of the cancer patient are to improve clinical outcomes maximize consistency, continuity, coordination, and cost-effectiveness of treatment and to foster better communication among clinicians. Furthermore, increased communication between a patient's oncologist, primary care physician, and cardiologist will help ensure proper management of cardiovascular risk factors, appropriate follow-up care, and risk-reduction interventions for the prevention of cardiovascular events associated with the use of chemotherapeutic regimens commonly used to treat cancer.. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN03-02.