This review describes major factors that, singly or together, influence the concentration and distribution of D-glucose in mammals, particularly in humans, with emphasis on rest, physical activity, and alimentation. It identifies areas of uncertainty: distribution and concentrations of glucose in interstitial fluid, kinetics and mechanism of transcapillary glucose transport, kinetics and mechanism of glucose transport via its transporters into cells, detailed mechanisms by which hormones, exercise, and hypoxia affect glucose movement across cell membranes, whether translocation of glucose transporters to the cell membrane accounts completely, or even mainly, for insulin-stimulated glucose uptake, whether exercise stimulates release of a circulating insulinomimetic factor, and the relation between muscle glucose uptake and muscle blood flow. The review points out that there is no compartment of glucose in the body at which all glucose is at the same concentration, and that models of glucose metabolism, including effects of insulin on glucose metabolism based on assumptions of concentration homogeneity, cannot be entirely correct. A fresh approach to modeling is needed.