The major effort to evaluate the effect of age on insulin secretion has consisted of measurements of plasma insulin levels, either fasting or in response to oral or intravenous glucose. This chapter highlights the methodological issues that must be faced in an effort to define the effect of age on the aspects of insulin metabolism. Most of the available information concerning the effect of age on glucose tolerance is derived from studies of man. The fact that the glucose intolerance of aging is associated with normal to elevated levels of circulating insulin led to the natural assumption that the cause of the glucose intolerance is resistance to the action of insulin. Demonstration of bimodality permits objective criteria to be used in the separation of patients at every age into two components: a lower component, presumed to consist of individuals with normal glucose tolerance, and an upper one, which includes patients with diabetes.