More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.