Until the last decade, the diagnosis of GH deficiency (GHD) in adults was only considered as a marker of hypothalamo-pituitary disease. GHD in adults is now recognized as a specific clinical syndrome associated with a cluster of cardiovascular risk factors such as altered body composition with increased body fat, insulin resistance, adverse lipid profile, reduced physical performance, reduced bone mineral density and impaired quality of life. Several randomized placebo controlled trials have now established that GH replacement can reverse some of these biological changes and improve the overall health status in GHD adults; as a consequence, GH replacement therapy has now been approved in many countries in such patients. With the advent of recombinant technology, there is a virtually unlimited, safe supply of recombinant human GH. Although GH replacement is not administered as commonly as steroid, thyroid and sex hormones in hypopituitary patients, a six-month trial of GH replacement with re-evaluation of well-being, body composition and lipid profile is currently recommended. However, there is marked individual variability in the response to GH replacement, with IGF-I being the most sensitive serum marker of GH action. Questions yet remaining to be answered relate to the role of GH replacement in cases of partial GHD and its use in the elderly population. The safety of long term replacement therapy remains an important issue, particularly in relation to the cardio-vascular system, the incidence of de novo malignant tumours and the recurrence rate of pituitary tumours. In the context of safety, it remains essential to monitor patients by means of longitudinal surveillance databases.