Research in recent decades has extended the realm of the endocrine system beyond the classical endocrine glands. Endocrine cells have been found in almost all organs or tissues within the body, with hormones being secreted from the gut, kidney, liver, heart and lung, and from the skin, bone, muscle and fat tissues. Indeed the adipose tissue, previously considered as an inert energy store, is probably the largest endocrine organ in the body. Since the identification of leptin as a fat-derived hormone or adipokine, a large number of adipokines have been identified through genomic and proteomics based strategies, and shown to impact on glucose and lipid metabolism, energy homeostasis and inflammation. Dysregulated secretion of various adipokines has been demonstrated in the obese state, leading to insulin resistance and chronic, low-grade, systemic inflammation which, at least in part, explain why obesity is responsible for 58% of the cases of diabetes and 21% of ischemic heart disease worldwide. Of the known adipokines, adiponectin and adipocyte fatty acid binding protein (A-FABP) have the highest circulating levels in humans and are biomarkers predictive of atherosclerotic diseases and/or type 2 diabetes, with increased risk being conferred by low adiponectin or high A-FABP levels. On the other hand, high levels of fibroblast growth factor 21 (FGF21), a liver-derived hormone with beneficial metabolic effects in animal studies, are found in obesity, suggesting the presence of FGF21 resistance. High FGF21 levels are also found in subjects with diabetes, dyslipidaemia, carotid and coronary atherosclerosis. Interestingly, FGF21 resembles some of the classical hormones in exhibiting a circadian rhythm and interacts with growth hormone as an endogenous regulator of lipolysis. Research on these metabolic hormones have improved our understanding of the pathogenesis of obesity-related pathologies and provided increasing evidence for their role as biomarkers and therapeutic targets for obesity-related cardiometabolic diseases.