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Mathematical models in the study of glucose metabolism, insulin secretion and the insulin-glucose interactions have a longstanding tradition. The recent advances in this area are reviewed, with particular emphasis on the methods for the assessment of insulin sensitivity and insulin secretion. The available models are illustrated, and their common aspects and differences discussed.For the assessment of insulin sensitivity and β-cell function, several modeling methods have recently been developed. Models for insulin sensitivity provide insulin-sensitivity indices from simple clinical tests, or a rich multiple-parameter characterization of insulin sensitivity from more elaborate experiments. Models for β-cell function yield indices that quantify the ability of the β-cells to respond to glucose stimuli. Furthermore, models of the insulin-glucose interactions propose interesting explanations of some experimental observations such as insulin-glucose oscillations and the progression to type 2 diabetes.Mathematical models in this area continue to evolve toward more accurate and clinically applicable approaches, and should be considered as a useful resource for clinical investigators. Models also have a potentially important role for understanding the mechanisms governing the insulin-glucose regulation system.