Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia Glucocorticoids are pleiotropic hormones with regulatory roles in fuel metabolism, immune defence, bone and connective tissue homeostasis as well as growth and development. Clinically, glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by significant adverse effects such as osteoporosis, diabetes and obesity. Recent insights into the mechanisms of action of both endogenous and exogenous glucocorticoids in bone cells have unlocked new potential approaches for the prevention and treatment of glucocorticoid-induced osteoporosis. Furthermore, studies in rodents indicate that the osteoblast-derived peptide, osteocalcin, plays a central role in the pathogenesis of glucocorticoid-induced diabetes and obesity. More recently, glucocorticoid signalling in bone cells has been found to be central in the regulation of aging-associated changes and high-fat diet induced changes in body composition and glucose metabolism. This presentation will review the glucocorticoid action and discuss emerging concepts regarding the molecular mechanisms underlying the adverse effects of glucocorticoid excess.