The pathogenesis of osteoporosis in chronic liver disease and post-liver transplantation is complex and heterogeneous. The development of hepatic osteodystrophy may be related to both increased bone resorption and decreased bone formation. Available medical treatments can be broadly classified into antiresorptive and bone-stimulating agents. Most published studies on the treatment of osteoporosis in patients with liver disease have used the commonly prescribed antiosteoporosis drugs approved for postmenopausal osteoporosis. These studies have included a small number of subjects and used bone mineral density (BMD) changes rather than fracture occurrence as an endpoint because of the short follow-up. Although the increases in BMD are promising, no intervention is proven to have antifracture efficacy in hepatic osteodystrophy. The natural history of bone disease following liver transplantation has not been fully investigated, although studies suggest that bone mineral loss is transient and generally reverses within a year following transplantation. The approach to treatment in liver transplant recipients should be targeted at preventing the early bone loss without interfering with the later recovery. Based on the available data, no single available agent can be considered as first-line therapy. In our opinion, the best treatment approach involves the elucidation of modifiable risk factors and the selection of agents targeted at the underlying derangements.