This paper reviews the findings accumulated on the role of melatonin (MEL) on bone status and the role of RANKL/RANK/OPG system (receptor activator of nuclear factor-kappa B ligand/ receptor activator of nuclear factor-kappa B/osteoprotegerin) in this mechanism. Recent studies indicate that MEL may influence on the bone directly by acting osteoclasts and perhaps osteoblasts, and/or indirectly by down-regulating RANK-mediated osteoclast formation and activation. Induced by MEL, changes in the level of factors which play a role in the regulation of bone remodelling, may secondarily (directly and/or indirectly through RANKURANK/OPG system) influence on bone status.