Homeostasis of blood glucose is the central tenet of metabolic disease and its treatment. This nonlinear dynamics problem is an obvious application of mathematical modeling. In particular, the practical questions of pharmaceutical research and development has offered several opportunities to bring modeling to an enterprise that is only recently accepting quantitative approaches on an equal footing with empirical approaches. Mathematical modeling of metabolic disease will be discussed in the context of pharmaceutical development from target discovery to translation of animal models informing clinical design to drug registration PK/PD.