Therapeutic inhibition of the vascular endothelial growth factor (VEGF) signaling pathway (VSP) is increasingly employed in the contemporary treatment of many cancer types. VSP inhibitors include the anti-VEGF monoclonal antibody (bevacizumab), soluble VEGF receptors (VEGF Trap), and small molecule tyrosine kinase inhibitors (TKIs) targeting the intracellular kinase domain of VEGF receptors. These agents are associated with cardiovascular toxicities such as hypertension, thrombosis, myocardial ischemia, and left ventricular (LV) dysfunction. Data on VSP inhibitor-associated LV dysfunction are largely limited to retrospective studies. Prospective studies are needed to establish the clinical significance of VSP inhibitor-associated LV dysfunction in the general population. Pre-clinical models of VSP inhibitor-associated LV dysfunction have identified mechanisms of cardiotoxicity and may improve our understanding of the pathophysiology underlying other cardiomyopathies. This review provides an overview of LV dysfunction that can occur in patients treated with VSP inhibitors. Potential strategies for clinical detection and management of this cardiotoxicity are explored, while acknowledging that currently available data specific to VSP-inhibitor LV dysfunction are limited. Avenues for future research are suggested.