Over the last decade, molecularly targeted drugs have become established in oncology therapeutics and clinical research. While initially marketed as “cancer specific” agents with superior toxicity profiles to conventional anti-proliferative and DNA-damaging chemotherapy, it has become increasingly apparent that these drugs have numerous serious “on-target” and “off-target” adverse effects [1]. Cardiovascular events are one such toxicity, with wide-reaching and profound therapeutic implications. As we continue to strive for and achieve superior patient outcomes in terms of cancer-specific survival, the relevance of competing causes of patient morbidity and mortality such as cardiovascular toxicity rises [2]. The objectives of this review are to discuss hypertension, ventricular dysfunction and QTc prolongation as toxicities directly related to the administration of molecularly targeted agents in cancer patients, with the goal of enhancing the oncologist’s approach to and management of these increasingly common side effects.