Once considered a passive reservoir for lipid storage and an inert provider of thermal/mechanical insulation, white adipose tissue (WAT) is presently seen as a highly dynamic endocrine organ that actively modulates a variety of physiologic processes, including energy balance, food intake, inflammation, immunity, metabolism, as well as cardio-vascular (CV) and neuroendocrine homeostasis. Actually, other than fatty acids and lipid moieties, WAT secretes a wide range of bioactive factors, considerably different in therms of structure and functions, including cytokines, chemokines, growth factors, complement system molecules, acute phase reactants, and hormones, among which the products predominantly or exclusively synthesized by and released from adipocytes are categorized as "adipokines". The adipokine expression is intimately linked to various parameters of adiposity (such as total body fat, percentage of body fat, and fat distribution), resulting generally (with very few exceptions, such as adiponectin, omentin, and Zinc-alpha2-glycoprotein) in positive correlation with WAT mass. The adipokine profiles undergo opposite changes in WAT excess or deficiency/dystrophy. In obese subjects, the altered adipokine network strikingly contributes to the development of systemic low-grade inflammation, as well as of obesity-related metabolic/CV comorbidities, that collectively define the so called metabolic syndrome. Adipokine dysregulation has been also observed in patients with chronic inflammatory/autoimmune disorders, such as connective tissue diseases, and adipokine pathway targeting has been thought to represent a potential innovative therapeutic perspective. Comprehensive advances in understanding the WAT biology and signaling may provide crucial insights into the physiopathology of the whole body homeostasis.