Research investigations on adipose tissue were focused for several decades on its "storage" function. Emerging evidence unveiled adipose tissue as an endocrine organ releasing a several mediators termed as adipokines. Adipokine-mediated functions include both physiological and pathophysiological roles such as regulation of energy metabolism, immune response and vascular homeostasis, as well as inflammatory and metabolic diseases (i.e. atherogenesis, diabetes and obesity clustered in the concept of metabolic syndrome). A dysregulation of adipokine levels has been also suggested as a potential common mechanism underlying these disorders. For instance, an unbalance between pro- and anti-inflammatory adipokines was positively associated with traditional risk factors (dyslipidaemia, hypertension, insulin resistance) in obesity, diabetes and atherogenesis. Adipokine-mediated activities particularly affected endothelial dysfunction/activation and intraplaque inflammation/vulnerability. The purpose of this narrative review is to provide an overview on the role of adipokines in atherogenesis. Evidence from basic research studies about adipokine-induced regulation of vascular and immune cell subsets will be discussed. Finally, conflicting results from clinical trials we be reported, with an attempt to better understand the reason why promising basic research results did not allow a speedy "into human" translation for clinical management of atherogenesis.