The discovery of the osteoprotegerin, receptor activator of nuclear factor-kappa B ligand and receptor activator of nuclear factor-kappa B and identification of their role in osteoclastogenesis provided a major advance in bone biology. receptor activator of nuclear factor-kappa B ligand binds to its receptors on the surface of preosteoclasts and stimulates their differentiation into active osteoclasts, leading to bone resorption. Osteoprotegerin is a soluble decoy receptor for the receptor activator of nuclear factor-kappa B ligand thereby inhibiting bone resorption. In addition to providing fundamental insights in bone biology, they may be involved in the immune system, arterial calcification and a number of metabolic bone diseases. In this review, we summarize the roles of receptor activator of nuclear factor-kappa B, receptor activator of nuclear factor-kappa B ligand and osteoprotegerin in bone metabolism, immune system and arterial calcification and discuss their potential in the treatment of these diseases.