Osteoporosis, a multifaceted bone disorder, is considered as a serious health problem throughout the world and the magnitude of diseased patients is increasing day by day. A number of successful therapeutics is available in the market for treatment. However, upon long-term administration, most of these drugs cause side-effects with some limitations. Henceforth, development of new therapeutic strategies can be a way to solve this problem as well as to develop cost effective and better tolerated therapies. Detailed understanding about the mechanistic action of the drug targets can be a great aid in the drug development process. Here in this review, we discussed the existing potential protein target class and their inhibitors related to osteoporosis. We have highlighted the existing potential protein drug targets, oestrogen receptor, calcium sensing receptor, P2Y receptor, activin receptor, calcitonin receptor, therapeutic manipulation of protease class such as cathepsin K, targeting WNT/ β-catenin signaling and targeting RANK-RANKL signaling pathway, TNF inhibition through TNF receptor. We hope this detailed report will provide a better way of understanding towards the discovery and also for development of novel therapeutics. © 2013 Bentham Science Publishers.