Growth hormone (GH) has diverse metabolic actions that regulate body composition, fluid homeostasis, glucose and lipid metabolism, bone metabolism, exercise performance and cardiac function. These actions improve the quality of life of adults, and confer beneficial effects when adults with GH deficiency are treated with recombinant human GH (rhGH). These important findings and the regulation of the GH-insulin-like growth factor-I (GH-IGF-I) axis are reviewed in detail in this volume. Shortly after the development of radioimmunoassays for GH in the early 1960s, multiple factors such as age, gender, pubertal status, nutrition, sleep, body composition, stress, exercise and several hormones were found to regulate GH secretion (for early review see Reichlin, 1974). Subsequent research has demonstrated that GH is secreted in discrete pulses, separated by periods of secretory quiescence. The pattern of GH release may modulate its metabolic actions. The amplitude and frequency of GH secretory pulses are regulated by physiological factors via effects on the hypothalamus and by direct actions of various hormones and metabolites on the GH-secreting pituitary cells, the somatotrophs. The pituitary integrates these signals and releases GH in a precisely regulated manner to ensure that the correct amount of GH reaches its target tissues. Although GH deficiency is usually diagnosed in the setting of hypothalamic and pituitary disease, alterations in the central and peripheral signals that normally regulate GH may account for the relative GH deficiency observed with ageing and obesity. Understanding the mechanisms by which GH secretion is normally regulated may suggest strategies for enhancing endogenous GH secretion in states of relative GH deficiency. These strategies may include pharmacological approaches such as the use of GH secretagogues or modification of nutrition, sleep and exercise habits.