RANKL and its receptor RANK are master regulators of osteoclast development and could explain the multitude of diseases associated with bone loss. However, RANKL/RANK are also expressed in other tissues such as the brain where they control the central fever response or the mammary gland where RANKL/RANK are essential for the formation of a lactating mammary gland in pregnant females. Moreover, we have shown that RANKL/RANK link sex hormones to mammary cancer development opening up potential new avenues for breast cancer treatment and even breast cancer prevention. I will discuss the non-bone function of RANKL/RANK and introduce novel functions of RANKL/RANK in normal physiology and disease, in particular cancer.