Teriparatide, recombinant human parathyroid hormone (1-34) (rhPTH [1-34]), is approved for the treatment of osteoporosis in men and postmenopausal women at high risk for fracture. The best candidates are those who have already had vertebral compression fractures (symptomatic or asymptomatic) or other osteoporosis-related fractures, or those who have very low bone mineral density, in the T score range of -3.5 or below. Teriparatide is the first anabolic drug approved by the US Food and Drug Administration for osteoporosis. It not only dramatically improves bone mass, but also restores bone microarchitecture and increases bone diameter. All of these mechanisms contribute to increasing bone strength and reducing the risk for osteoporosis-related fractures. Although PTH has been used in combination with other agents such as estrogens, calcitonin, and bisphosphonates, the relative benefit of the combined approach versus teriparatide alone for fracture risk reduction has not been shown. In fact, some data suggest that initiating PTH and alendronate together in previously untreated patients or pretreating patients for a short time with alendronate before initiating PTH may somewhat reduce the anabolic response to PTH. There are many unanswered questions regarding PTH, such as the optimal duration of treatment, the optimal sequence of medications for severe osteoporosis, the mechanism of resistance to effect after 18 to 24 months, the effect of subsequent rechallenge with PTH and, most importantly, surrogates to measure PTH effect.