Vascular disease, exceedingly common in persons with long-term diabetes and affecting both large and small blood vessels, presents the greatest problem and challenge in diabetes today. Large vessel involvement is responsible for a frequency of cerebrovascular, coronary and peripheralvascular disease which is significantly greater in diabetic than nondiabetic individuals. However, most characteristic of diabetes is microangiopathy which, although widespread in the body, is seen most forcibly in the eyes (diabetic retinopathy) and kidneys (intercapillary glomerulosclerosis). Since treatment of fully developed complications is unsatisfactory, exploration of ways of prevention offers the best hope for the future. This leads the investigator and clinician alike into the origins of diabetes itself and the relationship of the metabolic defect (insulin deficiency) to vascular disease. That the tendency to diabetes is inherited is commonly accepted but knowledge is lacking as to exactly what the diabetic inherits. Environmental factors such as overnutrition, pregnancy, infections, steroid administration, etc., favor the emergence of the tendency to a state clinically recognizable. Special studies and clinical experience suggest that in the early stages of the diabetic state (“prediabetes” and “chemical diabetes”) there exists a fluid, dynamic condition in which not only progression but also remission are possible, therein affording hope for the eventual discovery of means of halting progression of the metabolic defect. Microvascular disease may be demonstrable (in the form of thickening of the basement membrane of small blood vessels) even in the early stages of the diabetic state. However, present knowledge does not warrant the conclusion that the tendency to vascular disease is inherited as a separate trait which develops independently of the tendency to the metabolic defect. On the contrary, there is increasing evidence to suggest that even in prediabetes the pancreatic release of insulin in response to glucose given intravenously may be subnormal, delayed or inappropriate in relation to the level of blood glucose at the time. With information currently available it is unwarranted to assume that vascular disease in its origin and development is unrelated to the metabolic defect. These considerations lead naturally into the matter as to whether the degree of control of diabetes, i.e., to which insulin deficiency is met, has any influence on the frequency, degree and time of appearance of the vascular sequelae. Evidence is presented from studies in nonhereditary diabetes both in man and animals, from general clinical experience and from special clinical studies, to support the view that there is, indeed, such a relationship and that by careful and consistent control of diabetes, complications may be lessened or delayed.