The current world epidemic of type 2 diabetes mellitus results from two general groups of causative factors. One is the influence of strong pathogenetic environmental pressures - also described as negative civilizational influence - on the very large subpopulation, assessed at 30% of the total world population, which is genetically predisposed to react to this external stress with the symptoms of type 2 diabetes mellitus. Such a pathogenetic reaction is based on the appearance of cellular and organ resistance to insulin. A second factor involves the beta cells of the pancreatic islets and their dysfunction. For these reasons, studies on the aetiology of insulin resistance have significance, both theoretical and practical. There are many biological deviations that can produce cellular insulin resistance and underutilization of glucose. The mechanism that is always present is the decrease of cellular glucose transport. For this reason, it should be approached as a potential target for preventive and therapeutic actions. These pathophysiological and clinical circumstances were the motivation for presenting a review of cellular glucose transport pathophysiology, which contributes to the aetiology of insulin resistance, cellular underutilization of glucose, and type 2 diabetes mellitus. They underline the significance of cellular glucose transport as a target for prevention and therapy of type 2 diabetes mellitus and other insulin resistant conditions. This review presents comments about the influence on cellular glucose transport of diet, physical exercise, and pharmacotherapeutic agents, based on the authors' studies. The review could contribute to an innovative approach to the pathogenesis, prevention, and therapy of type 2 diabetes mellitus and other conditions related to insulin resistance.