Blood glucose concentrations are required to be maintained within a narrow therapeutic range in order to ensure the normal functioning of the body. This is accomplished through a complex, interactive, finely coordinated neuro-endocrine regulatory process. Hormonal control through the opposing actions of insulin and glucagon secreted by the islet cells of the pancreas serve as the primary response mechanism to avert post-prandial hyperglycaemia and fasting hypoglycaemia. In addition to this basic response, a range of endocrine mediators concurrently intervene, to enable the fine modulation of the process through a range of insulin-dependent and insulin-independent processes, which ultimately achieve glycaemic control by influencing tissue glucose uptake, glycolysis, glycogenesis, glycogenolysis and gluconeogenesis. More recent evidence supports a central, predominantly hypothalamic role initiated through nutrient (glucose, fatty acid) and hormonal (insulin, leptin, glucagon-like peptide-1) stimuli that influences glucose regulation by direct or indirect effects on skeletal muscle glucose uptake, islet cell insulin/glucagon secretion and hepatic glucose production.