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Key Points The growth hormone (GH)insulin-like growth factor (IGF) axis consists of central neuro-anatomical, regulatory and genetic systems, and the peripheral intracellular GH signalling pathway The introduction of recombinant human GH (rhGH) in 1985 ended the phase of pituitary-derived human growth hormone (hGH) and its associated limitations and risks, opening the possibility of widespread clinical use GH deficiency (GHD) is a syndrome with many different causes and is associated with alterations in growth, body composition and metabolism In some non-GHD short stature disorders, rhGH has been proved effective and is used as a surrogate for the currently unknown, pathophysiologically appropriate treatment Risks of hGH therapy might relate to its direct effects on growth, its anti-insulin action and its cell-proliferating activity