Abstract Leptin is a hormone involved with satiety and energy balance and proposed to be an anti-obesity factor. Much effort has been dedicated to the relationship between leptin and bone. This interest stems from the knowledge that body weight is a major determinant of bone density. It is known that obese persons have stronger bones and lose bone tissue at a slower pace. Therefore, attention has been given to leptin as a mediator of increased osteogenesis. Leptin has been shown to play a role on bone both in vitro and in vivo.The administration of leptin in vitro induced the expression of leptin receptors on stromal cells, the differentiation to osteoblasts and inhibition of differentiation into the adipocyte phenotype. In addition, leptin was able to inhibit osteoclastogenesis of peripheral blood mononuclear cells. Therefore, there is in vitro and experimental evidence that leptin is able both to stimulate osteoblasts and inhibit osteoclast differentiation. This would be in line with the hypothesis that the correlation between obesity and increased BMD is linked to leptin activity. However, experimental results are indicative of a role of CNS in mediating the effect of leptin on bone metabolism. These effects are opposite to the direct effects on bone cells and lead to bone loss. To solve the problem, it has been suggested that obese individuals have a resistance of nervous structures to leptin. In chronic renal failure serum leptin levels are markedly increased. An inverse correlation between histomorphometric parameters of bone turnover and serum leptin levels and between leptin and PTH have been reported.Therefore, the hypothesis has been raised that leptin lowers bone turnover in chronic renal failure. Since leptin has a direct stimulatory effect on bone and an indirect opposite effect via the CNS, it has been suggested that in CRF a resistance of nervous structures to leptin, like in obesity, may be present. By now, coherent findings suggest that the prevailing effect of leptin on bone in ESRD is that of reducing bone turnover.