Bone is a dynamic tissue that undergoes continuous remodeling. It goes through a balanced process that entails repeated cycles of bone resorption coupled with synthesis of new bone matrix (Fig. 1). These remodeling cycles are influenced by an individual’s age, endocrine and nutritional status, and level of physical activity. This ongoing tissue turnover is important for meeting the often conflicting need of the skeleton to maintain structural support for the body while also providing a source of ions for mineral homeostasis. The maintenance of skeletal mass in the face of continuous bone remodeling requires the coordinated activities of osteoblasts and osteoclasts, the two cell types responsible for skeletal matrix formation and resorption (1) (Fig. 1). Advances in our understanding of the precise mechanisms that control the cellular interactions and coupled activities of these two cell types have provided new insight into a number of diseases affecting the skeleton. These disorders are characterized by an imbalance of remodeling with subsequent increase in bone resorption, decreased bone mass, and loss of skeletal stability and integrity. This is particularly true for neoplastic diseases, in which a number of common human malignancies have a propensity to spread to the skeleton, resulting in significant morbidity and mortality from bone destruction (2).