Organ transplantation has become increasingly common as a therapy for end-stage renal, liver, cardiac and pulmonary disease. The population of patients who have survived organ transplantation has grown dramatically over the last 2 decades. Although organ transplant recipients now benefit from greatly improved survival, long-term complications of organ transplantation, such as osteoporosis, adversely affect quality of life and must be addressed. In the early post-transplantation period, the effects of high dose glucocorticoids, combined with other immunosuppressive drugs such as cycosporine A and tacrolimus, cause rapid bone loss particularly at the spine and proximal femur. In this setting, fracture incidence rates as high as 25-65% have been reported. Treatment and prevention strategies must target this early post-transplant period, as well as the patient awaiting transplantation and the long-term transplant recipient. This review will discuss the clinical features of transplantation osteoporosis, the pathophysiology of post-transplantation bone loss and prevention and therapy of this unique bone disease.