Growth hormone (GH) was first isolated from cadaver pituitary glands, requiring laborious and expensive collection of glands, followed by extraction and purification of the hormone. This limited supply restricted its use to children with severe GH deficiency who were treated with low dosages and suboptimal schedules. The development of recombinant DNA-derived GH, allowed the production of virtually unlimited amounts of GH, leading to the approval for therapy for a large number of childhood conditions characterized by non-GH deficient short stature. The aim of this review is to provide a critical overview on the daily use of GH in two paradigmatic conditions of non-GH deficient short stature which are children born small for gestational age and with idiopathic short stature, highlighting the available strength of evidence for efficacy and safety.