Recombinant human IGF-I (rhIGF-I) has been approved as a therapeutic agent for short stature due to primary IGF-I deficiency following clinical trials that lasted more than 10 years. The first children treated with rhIGF-I were those with short stature resulting from defects in growth hormone (GH) action, either due to GH receptor abnormalities or the development of GH-neutralizing antibodies that arose following GH exposure. The administration of rhIGF-I to such children results in improvements in growth rate that are sustained over many years. This appears to improve adult height, but so far the effects are not as robust as when GH-deficient children are treated with human GH. Side effects are common but manageable and seldom necessitate discontinuation of therapy.