The TNF-family molecule osteoprotegerin ligand (OPGL, also known as TRANCE, RANKL and ODF) is a key regulator of bone remodeling and essential for the development and activation of osteoclasts. Intriguingly, OPGL also regulates T cell-dendritic cell communications, dendritic cell survival and lymph-node organogenesis. Here, Young-Yun Kong and colleagues discuss the role of OPGL, and its receptor RANK, in the immune system and in bone metabolism.