Insulin-like growth factors (IGF) are key players in regulating growth and development of pre- and postnatal tissues. In addition, insulin-like growth factor-1 (IGF-1) known to be a key stimulus of placental substrate uptake inhibits fetal placental catabolism and reduces placental lactate production. Insulin-like growth factor-1 receptor (IGF-1) deletions cause intrauterine failure to thrive. IGF-1R gene knockout experiments have revealed a mild pre- and postnatal growth deficit in heterozygous IGF-1R+/- mice. A gene dosage effect of the IGF-1R gene on embryonic and postnatal growth, and also on postnatal growth of tissues and organs has been investigated in clonal mice strains with a wide spectrum of IGF-1R deficiency. Approximately 10% of infants with intrauterine growth retardation (IUGR) remain small, but the causes remain unknown. Recently, monoallelic loss of chromosome 15q, mutations of the IGF-1 receptor gene, and loss of one copy of the IGF-1 receptor gene again owing to deletions of the distal long arm of chromosome 15 have been found in patients with intrauterine growth retardation and postnatal growth deficit. Binding of IGF-1 to erythrocytes in short children with IUGR has shown to be lower than in children with normal height. The number of IGF-1 receptor copies on human fibroblasts seems to be predictive of their proliferative response to IGF-1. Hemizygosity for IGF-1R can cause primary IGF-1 resistance despite normal or even elevated GH and/or IGF-1 serum concentrations. At present IGF-dependent growth in prenatal life seems to be largely independent of GH, except for a small effect just before birth, while IGF-dependent growth after birth and particularly during puberty is strongly related to growth hormone (GH) action. In conclusion, mutations and deletions of the IGF-1 receptor gene lead to abnormalities in the function and/or number of IGF-1 receptors. Alterations of the IGF-1 receptor signaling pathway seem to retard intrauterine and postnatal growth in humans. In the future, expression of such mutations in cells in vitro provides an opportunity to define the role of IGF-1 receptor in human growth and growth disorders.