Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the known incretin hormones in humans, released predominantly from the enteroendocrine K and L cells within the gut. Their secretion is regulated by a complex of integrated mechanisms involving direct contact for the activation of different chemo-sensors on the brush boarder of K and L cells and several indirect neuro-immuno-hormonal loops. The biological actions of GIP and GLP-1 are fundamental determinants of islet function and blood glucose homeostasis in health and type 2 diabetes. Moreover, there is increasing recognition that GIP and GLP-1 also exert pleiotropic extra-glycaemic actions, which may represent therapeutic targets for human diseases. In this review, we summarise current knowledge of the biology of incretin hormones in health and metabolic disorders and highlight the therapeutic potential of incretin hormones in metabolic regulation.