Nowadays it is well known that testosterone induce a spectacular hypertrophy of skeletal muscle. Due to their strong myotrophic action and despite their serious and irreversible side effects, anabolic steroids are widely used among athletes and also subjects who simply want to improve their appearance. Randomized, placebo-controlled studies clearly show that the administration of supra-physiological doses of testosterone in untrained and trained subjects produces a significant increase in muscle strength and in the cross-sectional area of skeletal muscle (1). Important mechanisms behind the myotrophic effects of testosterone on skeletal muscle were uncovered for the first time in a population of power lifters who have reported the use of testosterone (100 to 500 mg/week) in combination to a wide variety of anabolic steroids for a period of 9 ± 3,3 years (2). Long-term steroid usage accentuates the degree of fibre hypertrophy in already well-trained power-lifters (2). In steroid users, the elevated myonuclear content together with the strong correlation between fibre area and the number of myonuclei (r = 0.86 ; p< 0.0001) suggested for the first time that a main mechanism by which testosterone exerts its myotrophic effect is to enhance the proliferation of satellite cells which is followed by myonuclear accretion (2). All the findings observed in skeletal muscle of long-term steroid users were subsequently confirmed in well-controlled short-term studies where subjects were given supra-physiological doses of testosterone (1). Satellite cells in skeletal muscle represent a population of stem cells located between the plasma membrane and the basal lamina and are capable of entering the cell cycle to generate daughter cells, which can either become new myonuclei or fuse together to form new myofibres that can fuse with existing muscle fibres (1). In this respect, skeletal muscle of long-term steroid users is characterised by a high frequency of fibres with centrally located myonuclei and also fibres in instance of fusing together (2). It is important to note that myonuclear addition would occur only when existing myonuclei become unable to sustain the growth of the muscle fibre (ceiling size concept) (1). In addition to the alterations in the nuclear machinery, testosterone also increases net protein synthesis and reutilization of intracellular amino acids in skeletal muscle (3). When satellite cells proliferate, some daughter cells may escape differentiation and remain quiescent (1). In this respect, in long-term steroid users, the number of satellite cells is similar to that counted in well-trained athletes but is higher to that found in untrained subjects (2). However, further studies are warranted to examine the regenerative capacity of long-term steroid users. In addition to its effects on satellite cells, it is also suggested that testosterone favours the commitment of pluripotent precursor cells into myotubes and decreases the number of adipocytes by down regulating key transcription factors involved in the adipogenic differentiation (4). The effects of testosterone on skeletal muscle are thought to be mediated via androgen receptors. When the hormone-receptor complex is translocated to the hormone responsive element within the nucleus it induces an increase in the rate of transcription. In normal resting skeletal muscle, androgen receptors are expressed in some but not all myonuclei (2), and within the same subject, differences in androgen receptor content exist between the trapezius and the vastus lateralis muscles (2). The amplitude of changes in androgen receptor content following training is also muscle dependent (1). Androgenic-anabolic steroids may either up-regulate or down regulate androgen receptor content. Long-term self-administration of steroids in humans is associated with increased androgen receptor-containing myonuclei in the trapezius but not in the vastus lateralis (2) indicating that in humans, the effects of testosterone can vary between muscles. In this respect, testosterone action might also be mediated through an androgen receptor independent pathway as it has been shown that testosterone stimulates G protein–linked membrane receptor at the plasma membrane resulting in a calcium dependent phosphorylation of a member of the MAPK family (5). Clearly, further studies are warranted to better understand the molecular pathways behind the physiological and supra-physiological action of testosterone on skeletal muscle.