GLUT-4 is the major insulin-sensitive glucose transporter in muscle and adipose tissue. Regulation of GLUT-4 is an important component of whole body glucose homeostasis. Abnormalities in the regulation of insulin-stimulated reversible translocation of glucose transporters have been observed in various pathological states, including diabetes. Recently, the development of specific photolabels for glucose transporters and the availability of antibodies against the various transporter isoforms have presented the opportunity for detailed kinetic analysis of GLUT-4 regulation. A kinetic analysis of some of the most recent data is presented to demonstrate how this approach can advance the understanding of GLUT-4 regulation. Some areas in which the currently available data limit the ability to resolve certain mechanistic questions are noted. Using a two-compartment model, we show that the mechanism of insulin-stimulated GLUT-4 translocation is likely to involve a large increase in the exocytosis rate of GLUT-4 with a minimal decrease in the endocytosis rate. Mathematical models based on these kinetic analyses are helpful for testing hypotheses and designing experiments to elucidate the molecular and cellular mechanisms of GLUT-4 regulation under normal and pathological conditions. This type of approach may be useful for evaluating the contribution of GLUT-4 regulation to the pathogenesis of diabetes.