Insulinlike growth factor-I (IGF-I) displays considerable structural and functional homology to insulin, as does its cognate receptor, which appears to utilize signal transduction molecules similar if not identical to those of the insulin receptor. Over the past several years, major emphasis has been placed on defining the range of biologic effects of IGF-I in vivo and in determining the physiologic consequences of interaction of IGF-I with a range of specific serum carrier proteins, the IGF binding proteins. Although early studies enrolled mainly healthy volunteers, recent studies have addressed the potential role of recombinant human IGF-I (rhIGF-I) as a therapeutic agent in a variety of clinical syndromes of altered carbohydrate homeostasis, including severe insulin resistance and types I and II diabetes mellitus. Initial studies demonstrated considerable efficacy for all of these conditions but raised concerns over the potential short-term toxicity of rhIGF-I, particularly in older individuals. Recent studies have concentrated on defining the doses of rhIGF-I that are well tolerated and provide therapeutic efficacy. Work also has concentrated on defining rhIGF-I's mechanisms of action. These more recent studies raise the possibility that rhIGF-I will be a useful addition to the treatment of diabetes mellitus.