Molecular inhibition of the epidermal growth factor receptor (EGFR) is a promising anticancer strategy and monoclonal antibodies (mAbs) to EGFR are undergoing extensive evaluation in preclinical and clinical trials. EGFR is frequently over expressed in many types of human malignancy and may be associated with prognosis, disease stage and survival. Therefore, EGFR represents an attractive target for cancer therapy. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Although rare, cardiac toxicity is a significant complication associated with cetuximab and the clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal events. This review aims to highlight an important albeit inadequately studied toxicity related to EGFR mAbs. We shall review preclinical and clinical literature to ascertain the etiology, incidence and management of cardiovascular complications of monoclonal antibodies to EGFR. As the potential clinical applications for these agents increase, clinicians using these agents need to remain vigilant regarding cardiovascular complications, especially in view of an aging cancer population.