Growth hormone (GH) and intracellular STAT 5 signalling represents a very old regulatory system and, whereas insulin dominates periprandially, GH may be viewed as the primary anabolic hormone during stress and fasting. GH exerts metabolic effects both directly and through stimulation of IGF-I, insulin, and free fatty acids (FFA). When well nourished the GH-induced stimulation of IGF-I and insulin is important for tissue anabolism whereas during fasting and other catabolic states GH predominantly stimulates the release and oxidation of FFA which leads to decreased glucose and protein oxidation and preservation of LBM. The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels. In the periprandial and postabsorptive states the effects of GH on protein metabolism are modest and include increased protein synthesis and decreased breakdown at the whole body level and in muscle together with decreased amino acid degradation/oxidation and decreased hepatic urea formation. During fasting and stress the effects of GH on protein metabolism become more pronounced; lack of GH during fasting increases protein loss and urea production rates by approximately 50% with a similar increase in muscle protein breakdown. The importance of GH is further substantiated by the observations that adult patients with GH-deficiency are obese and have reduced LBM, and impaired physical performance and acromegaly is characterised by increased LBM and decreased fat mass.