Short children born small-for-gestational-age (SGA) appear to be at an increased risk of having a poly-endocrinopathy, including a degree of growth hormone (GH) deficiency and/or insulin-like growth factor 1 (IGF-1) resistance. Among GH-deficient children, those born SGA present a lower growth response to GH therapy than those not born SGA. The growth response of short SGA children to GH treatment does not appear to depend significantly on the secretory status of GH (as judged by provocative testing), indicating that the SGA condition (IGF-1 resistance) predominates over the availability of endogenous GH in determining the short stature of the majority of these children. When a higher than replacement dose of GH is administered, the growth response of short SGA children matches that of GH-deficient non-SGA children, indicating that the IGF-1 resistance towards growth can be overcome, and that a normal stature can be obtained, at least throughout childhood. It is anticipated that, increasingly, the indications and the doses for GH therapy in children will become interlinked with the emerging principles of endocrine programming in early life.