As melatonin is not yet clinically used for osteoporosis and concerns about the current treatments' side effects remain, this review highlights its role in modulating osteoblast and osteoclast interactions, particularly through regulation of the receptor activator of nuclear factor‐κB ligand and osteoprotegerin, to achieve bone‐forming and antiresorptive effects. The gene discussed is TNFRSF11B; the disease is osteoporosis.