Bone turnover is much important in normal homeostasis of body skeleton. Medications, nutritional status, and systemic illnesses may affect bone metabolism by altering biochemical mediators. Prostaglandins, especially of E and F series are much important in bone physiology by affecting osteoclastic activity and osteoblastic differentiation. In bone fracture, production of prostaglandins affects fracture healing. There is the possibility that non-steroidal anti-inflammatory drugs (NSAIDs) affect bone health by inhibiting cyclooxygenase (COX) enzymes which reduce synthesis of prostaglandins. The aim of this paper is to review the effects of NSAIDs on bone by evaluating both animal and human studies. Using key words such as bone, bone marker, bone mineral density, NSAIDs, COX inhibitor, bone metabolism and search engines like Web of sciences, Scopus, Pubmed, and Google scholar, all relevant studies were collected. Although NSAIDs showed anti-resorptive properties in animal studies and some few human studies, to date no conclusive result has been observed in bone formation. Some limited studies reported higher bone mineral density in daily users of NSAIDs.