The integrated glucose-insulin model was originally developed on a variety of intravenous glucose provocation experiments in healthy volunteers and type 2 diabetic patients. The model, which simultaneously describes time-courses of glucose and insulin based on mechanism-based components for production, elimination and homeostatic feedback, has been further extended to oral glucose provocations, meal tests and insulin administration. The model has been used to describe experiments ranging from 4 to 24 hr. Applications of the integrated glucose-insulin model include the clinical assessment of the mechanism of action of anti-diabetic drugs and the magnitude of their effects. Finally, the model was used for optimizing the design of provocation experiments.