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Growth hormone (GH) is a highly dynamic hormone, influencing growth and metabolism. GH secretion varies with biological maturity and nutritional state, illness, stress, and physical activity. GH deficiency (GHD) may be observed in the neonatal period or later throughout life. Thus, knowledge on normal physiology is necessary. Before any GH investigation, other conditions interfering with GH secretion or action must be ruled out. GH stimulates liver secretion of IGF-I and IGFBP-3; their serum concentrations may give information on the GH/IGF-I axis. GH investigation can be performed by stimulation tests or by estimating spontaneous GH secretion. If GHD is diagnosed, substitution therapy is possible. However, dosing is complicated by individual responsiveness to both GH and IGF-I, and possibly also varies with the growth phases. Auxological and biochemical variables associated with GH responsiveness have been retrieved from large cohorts of GH-treated children. There are models for prediction of growth response, indirectly informing us on individual responsiveness that can guide GH dosing from the start of treatment. More than 30 years of GH treatment have shown satisfactory safety, although the age of treated subjects and time for follow-up make continued follow-up studies necessary.