The circulating FGFs are a new group of proteins believed to function as classic hormones. With emphasis on human metabolism, we critically review current data, and propose that--although a number of questions remain--circulating FGF23 is pivotal in the control of phosphate and vitamin D metabolism, and may have additional systemic effects, particularly in chronic kidney disease; that FGF19 signaling is important for the regulation of bile acid metabolism, whereas its physiological role in promoting glucose and lipid metabolism is less well understood; and that the physiological role of circulating FGF21 in metabolic homeostasis warrants further investigation.
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