Vitamin D is a target of chronic exposure to glucocorticoid excess, which is the cause of a severe form of secondary osteoporosis. Glucocorticoids affect Vitamin D metabolism at different levels of the enzymatic cascade, thereby decreasing the synthesis of active Vitamin D and impairing its biological action at the tissue level. Moreover, glucocorticoids may directly counteract peripheral effects of Vitamin D, decreasing intestinal calcium absorption and favoring renal calcium loss with consequent negative calcium balance. Therefore, the use of Vitamin D and calcium is mandatory in patients exposed to glucocorticoid excess, although some peculiarities of this treatment should be taken into account to avoid under-treatment of hypovitaminosis D in the specific clinical context of glucocorticoid-induced osteoporosis. This chapter deals with pathophysiological, clinical, and therapeutic aspects of hypovitaminosis D in patients exposed to glucocortoicoid excess. © 2018 S. Karger AG, Basel.