Perivascular adipose tissue (PVAT) and its adipokines engage in bidirectional crosstalk with the vascular wall. Atherosclerosis disrupts this interaction through inflammation, rupture-prone plaques, and subsequent thrombosis. The cardioprotective effects of ghrelin are in contradiction to its adipogenic properties. The concurrent research of anti-/pro-atherogenic mechanisms of ghrelin and PVAT-derived adipokines provides a better understanding of atherosclerosis progression in metabolic disorders. In-depth coverage of the characteristic features of PVAT concerning vascular dysfunction, with a survey of ghrelin-induced anti-inflammatory effects on adipose tissue macrophage infiltration and the inhibitory activity of ghrelin on the proinflammatory adipokine secretion, show that the impact of ghrelin on the endothelial function should be studied in relation to PVAT.