Abstract We aimed to revise the increasingly accruing data about the association between anti-tyrosinkinase, “targeted” cancer drugs and the development of arterial thrombotic events or acute coronary syndromes. Further insights into the involved pathophysiologic mechanisms, and into the clinical implications are overviewed. Antiangiogenesis has become a mainstream of cancer therapy, leading to development of a specific class of drugs. Besides, a “wider” angiogenesis network made up of several growth factors, can be recognized as target of a higher number of compounds. Their widespread use has been progressively favored over conventional chemotherapy, because of their better safety/efficacy profile, even allowing a prolonged administration. However, there is a growing awareness of an association between these useful drugs and serious cardiovascular side effects including myocardial infarction, stroke, heart failure and cardiovascular death, in addition to the known relation with the most frequent hypertension onset. Observational studies indeed report that combined cardiovascular events may reach figures of 20–40%, and, for their management, several monitoring, diagnostic and therapeutic regimens have been suggested. On the basis of the available data we recommend an active screening program for acute coronary syndromes in the “at risk” period, immediately after the beginning of the “targeted” drug therapy, and during the whole administration time. Likewise, a mandatory cardiological specialistic evaluation is warranted to plan a schedule of follow-up evaluations for diagnostics, including ECG, echocardiogram, and multimarker evaluation. An appropriate treatment with antiplatelet or anticoagulant drugs, endothelial protective agents or cardiovascular interventions is similarly advised.