The growth hormone (GH) – insulin like growth factor I (IGF-I) axis plays a major role in the regulation of post natal growth. Overexpression of GH and IGF-I in mice leads to an overall increase in body size whereas animals deficient in GH or IGF-I are much smaller than their wild type counterparts. In humans, GH deficiency in adulthood is associated with decreases in lean body mass, of which skeletal muscle is a major component, and muscle strength. Long term GH administration is effective in increasing muscle mass and strength in these GH deficient patients. The effects of GH are classically thought to be mediated by IGF-I. Indeed, IGF-I expression in many tissues, including human skeletal muscle, is regulated by GH. Both GH and IGF-I exert their effects on growth and metabolism by interacting with specific receptors which are ubiquitously expressed in the tissues of the body. The mechanisms by which GH and IGF-I regulate muscle mass are complex and involve processes such as protein synthesis and the proliferation, differentiation, and survival of satellite cells. A key consideration is whether GH exerts its effects on skeletal muscle independently of IGF-I, as it is now recognized that GH has direct actions mediated by the GH receptor in many tissues including muscle. Further complexity arises from the fact that various isoforms of GH and IGF-I exist, but the precise biological role of each of these isoforms remains to be established. In addition, a number of other proteins, in particular IGF-I binding proteins (IGFBPs), affect the bioavailability and activity of their ligands. GH is currently administered as a therapeutic agent for the treatment of muscle wasting secondary to AIDS and cancer, and therapeutic approaches for IGF-I are being developed. The effectiveness of these agents in preventing muscle loss and/or increasing muscle mass in disease states has led to their use by normal individuals attempting to manipulate their muscle mass. There is, unfortunately, substantial anecdotal evidence for the widespread use of GH, and possibly IGF-I, by body builders as well as other athletes, a practice known as doping. Despite this, most of the data obtained under controlled experimental conditions does not show performance or muscle mass gains following GH administration in adults with normal GH endocrinology. Nevertheless, the use of GH as well as IGF-I is banned by the World Anti Doping Agency. As a result, considerable resources are being invested in the development of methods to detection of the use of recombinant human GH (rhGH). This is challenging because rh GH is essentially identical to the endogenously produced 22kD isoform of the hormone. Current strategies for the detection of rhGH administration rely on alterations in the ratio of 22kDa to other naturally occurring isoforms and the use of indirect markers of GH administration such as IGF-I and metabolites of bone and collagen turnover.