Although glucocorticoids are highly effective in the treatment of autoimmune inflammatory diseases, their use is limited by significant adverse outcomes including diabetes, sarcopenia and osteoporosis. Recent insights into the skeletal mechanisms of glucocorticoid action have identified osteoblasts and osteocytes as their main target cells in bone. At supra physiological levels, glucocorticoids suppress osteoblastogen-esis and osteoblast function, induce osteoblast cell cycle arrest and apoptosis and re-direct mesenchymal stem cell differentiation towards the adipocyte lineage. More recently, disturbances in the lacunar-canalicular system and reduced osteocyte viability have been identified to also negatively affect skeletal health during glucocorticoid therapy. As the predominant active mechanism in glucocorticoid-induced osteoporosis is the suppression of bone formation, concerns have been raised about the long-term use of anti-resorptive agents in these patients. Thus, osteo-anabolic treatments such as Teriparatide, which stimulate osteoblast activity and bone modelling, may be better suited to address the pathomechanism underlying glucocorticoid-induced osteoporosis. In regards to the metabolic adverse effects of glucocorti-coids (i. e. insulin resistance, diabetes), recent studies in rodents have indicated that the bone-derived peptide, osteocalcin, may play a role in mediating some of these outcomes. These findings link the detrimental effects of glucocorti-coids on energy metabolism directly to their suppressive actions on bone cells. In this article, we review the pathophysiology of glucocorti-coid action on bone cells, and discuss current and novel concepts regarding the cellular mechanisms underlying adverse effects of glu-cocorticoids such as osteoporosis and diabetes.