Katharina Urschel,1 Iwona Cicha2 1Laboratory of Molecular Cardiology, Department of Cardiology and Angiology, 2Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine, ENT Department, University Hospital Erlangen, Germany Abstract: Signaling pathways induced by the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) play a key role in the cellular responses to inflammation and injury. In the cardiovascular system, TNF-α -activated signal transduction pathways may contribute to vascular dysfunction, development and progression of atherosclerosis, and adverse cardiac remodeling following myocardial infarction and heart failure. This review addresses the role of TNF-α in vascular physiology and disease. Furthermore, the therapeutic benefits of systemic TNF-α antagonism in cardiovascular and autoimmune inflammatory diseases are summarized and critically discussed. Keywords: TNF-α, vascular inflammation, atherosclerosis, shear stress, heart failure, TNF-α antagonists