Osteoporosis, the most commonly occurring bone disease, is characterized by enhanced bone fragility and increased risk of fracture. Bone remodeling is the process in which bone is broken down by osteoclasts and then built back again by osteoblasts. In healthy adult bone, these two processes are balanced and a constant level of bone mass is maintained. Some of the proteins involved in the interaction between osteoblasts and osteoclasts have recently been identified. Receptor activator of nuclear factor-kappaB (RANK) ligand is produced by osteoblasts and exerts its effects through binding to its receptor (RANK) on osteoclast precursor cells. Binding results in activation of osteoclasts. Osteoblasts also produce osteoprotegerin (OPG), a potent inhibitor of osteoclast formation and a decoy receptor for RANK. The relative ratio of OPG and RANK ligand in the bone marrow microenvironment may determine the number of active osteoclasts, bone resorption rate, and bone mass. OPG is currently under investigation for osteoporosis treatment.