Adipose tissue is an active endocrine and paracrine organ that may influence the development of atherosclerosis and vascular disease. In the setting of obesity, adipose tissue produces a variety of inflammatory cytokines (or adipokines) that are known to modulate key mechanisms of atherogenesis. In particular, adipose tissue located on the surface of the heart surrounding large coronary arteries (i.e. epicardial perivascular adipose tissue) has been implicated in the pathogenesis of coronary artery disease. The present review outlines our current understanding of the cellular and molecular links between perivascular adipose tissue and atherosclerosis with a focus on potential mechanisms by which epicardial perivascular adipose tissue contributes to obesity-related coronary disease. The pathophysiology of perivascular adipose tissue in obesity and its influence on oxidative stress, inflammation, endothelial dysfunction and vascular reactivity is addressed. In addition, the contribution of specific epicardial perivascular adipose-derived adipokines (e.g. leptin, adiponectin) to the initiation and expansion of coronary disease is also highlighted. Finally, future investigative goals are discussed with an emphasis on indentifying novel therapeutic targets and disease markers within perivascular adipose tissue. Linked Articles This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit © 2011 The British Pharmacological Society.