Experimental data support a role for insulin and insulin-like growth factor-I (IGF-I) in the pathophysiology of vascular complications in diabetes. Clinical data for both hormones are less convincing, mainly because the various studies vary in methodologies, sample sizes, and populations. So far, by epidemiological means, insulin's vascular toxicity has been shown only in middle-aged non-diabetic men. Furthermore, serious methodological problems hamper the clear understanding of IGF-I's significance in this context. Definitive determination of the role of insulin, IGFs and other growth factors in the development of diabetic vascular complications needs considerably more work. In any case, hyperinsulinemia is associated with a cluster of other accepted risk factors for cardiovascular disease which altogether resemble the entire insulin-resistance syndrome.