The risk of fracture is intimately linked to loss of bone mass. The two most common pharmaceutical agents used to alter this loss are bisphosphonates and recombinant human parathyroid hormone (rhPTH 1-34; teriparatide). These two classes of drugs work through distinctly different mechanisms. Bisphosphonates bind to bone mineral and inhibit osteoclast activity. This leads to a reduction in bone remodeling, which slows bone loss, and also leads to significant changes in the bone material properties such as mineralization, microdamage, and the organic matrix. The long-term effects of these altered material properties are unclear. There are also noteworthy differences among the various bisphosphonates used clinically such as the speed of onset and magnitude of remodeling suppression. PTH is an anabolic agent which stimulates both remodeling and modeling—resulting in the formation of new bone which over time leads to an increase in bone mass. PTH also alters the material properties although these changes are distinctly different from the bisphosphonates. Recent studies have begun to investigate combining bisphosphonates and PTH, either sequentially or concomitantly, with most data showing that bisphosphonates blunt the full effect of PTH. Although bisphosphonates and PTH each have their own specific profile, mechanisms of action, and effects on bone mass, architecture and tissue properties, both have been shown to effectively reduce vertebral and non-vertebral fractures and improve the health of postmenopausal women and older men.