Glucose effectiveness (SG) is the ability of glucose per se to stimulate its own uptake and to suppress its own production under basal/constant insulin concentrations. In an individual, glucose tolerance is a function of insulin secretion, insulin action and SG. Under conditions of declining insulin secretion and action (e.g. type 2 diabetes), the degree of SG assumes increasing significance in determining the level of glucose tolerance both in fasted and postprandial states. Although the importance of SG has been recognized for years, mechanisms that contribute to SG are poorly understood. Research data on modulation of SG and its impact in glucose intolerance is limited. In this review, we will focus on the role of SG in the regulation of glucose tolerance, its evaluation, and potential advantages of therapies that can enhance glucose-induced stimulation of glucose uptake and suppression of its own production in conditions of impaired insulin secretion and action.