Secondary causes of bone loss are not often considered in patients who are diagnosed as having osteoporosis. In some studies, 20% to 30% of postmenopausal women and more than 50% of men with osteoporosis have a secondary cause. There are numerous causes of secondary bone loss, including adverse effects of drug therapy, endocrine disorders, eating disorders, immobilization, marrow-related disorders, disorders of the gastrointestinal or biliary tract, renal disease, and cancer. Patients who have undergone organ transplantation are also at increased risk for osteoporosis. In many cases, the adverse effects of osteoporosis are reversible with appropriate intervention. Because of the many treatment options that are now available for patients with osteoporosis and the tremendous advances that have been made in understanding the pathogenesis and diagnosis of the condition, it is important that medical disorders are recognized and appropriate interventions are undertaken. This article provides the framework for understanding causes of bone loss and approaches to their management.