There is a growing body of evidence that the insulin-like growth factors (IGF-I and IGF-II) are dynamically involved in the regulation of glucose homeostasis, with one of their binding proteins, IGFBP-1, playing a counterregulatory role. The IGFs are structurally and functionally related to insulin and in the circulation they represent a huge hypoglycemic potential which is buffered by their association with the IGFBPs. The predominant IGFBP in serum, IGFBP-3, is able to form a high molecular weight complex with the IGFs and this complex is retained in the circulation and appears to act as a reservoir of IGFs. The IGFs and IGFBP-3 are regulated in the long term by changes in nutritional status. In contrast, IGFBP-1 is acutely regulated in a manner similar to glucose counterregulatory hormones. IGFBP-1 is able to block the insulin-like actions of the circulating IGFs and when administered alone as a bolus infusion causes an increase in blood glucose levels. There is recent evidence that more IGFs are available for an endocrine glucoregulatory role than indicated by estimates of steady-state 'free' IGF levels. The IGF/IGFBP system may thus play a complementary role to insulin and the classical counterregulatory hormones in the control of blood glucose.