Glucocorticoid (GC)-induced osteoporosis (GIO) is a common and serious complication of prolonged systemic GC use. Bone loss with risk of fractures resulting from GC therapy is a relatively common disorder, and is the most prevalent form of secondary osteoporosis. It is generally accepted that GC can cause a rapid bone loss, decreasing bone formation and increasing bone resorption in vitro as well as in vivo. The decrease in bone formation has been mainly attributed to GC effects on osteoblastogenesis and osteocyte apoptosis, while the increase in bone resorption has been referred to an extension of the life-span of pre-existing osteoclasts. This article focuses on newer molecular aspects regarding the apoptotic mechanisms involved in the pathogenesis of GIO and is based on a presentation that was held at the 3rd Congresso Nazionale in Osteoporosi Secondarie e Endocrinopatie, in Ancona, Italy, October 2007.