Insulin-like growth factor I (IGF-I) has many potential therapeutic uses because of its varied effects--growth promotion, insulin-like influence on glucose metabolism, and neuroprotection resulting from cell-proliferative and antiapoptotic properties--but they have not been investigated systematically in clinical situations. The growth-promoting effect of recombinant human IGF-I (rhIGF-I) in the extensively studied growth hormone insensitivity syndrome (GHIS; Laron syndrome) signifies an endocrine role for the GH-IGF system. The metabolism of (adult) patients with severe insulin resistance is improved by rhIGF-I, which--together with insulin therapy--also improves metabolic control in type 1 and 2 diabetes. Further studies on IGF-I metabolic effects and growing understanding of the IGF-I-IGF-binding protein system could open new therapeutic avenues.