The RANK, RANKL and OPG interaction plays a major role in bone resorption and remodelling. The history dates back to mid 1990s when the RANK/ RANKL interaction was found to mediate osteoblastic stromal cells to stimulate osteoclastic bone resorption. This interaction was found to induce several cytokines including the TNF superfamily, thereby activating the pathways of bone remodelling. The Osteoprotegerin (OPG) prevents the binding of RANKL to RANK, thereby preventing the excessive bone resorption. When there is an imbalance in the levels of RANK/RANKL/OPG, the metabolic activity of the bone cells gets altered and thus there is loss of balance between bone formation and resorption. Thus, studying the inter – relationship between RANK, RANKL and OPG becomes critical for assessing the osteoblastic and osteoclastic activity.