Clinical data suggested that parathyroid hormone (PTH) might be effective in improving bone mass in patients with osteoporosis, providing its resorptive effects, which are particularly marked at cortical sites, were kept under control. We reviewed the evidence that intermittent PTH therapy is a valid treatment option whose predominant effect is bone anabolism. In cell culture studies, PTH affected both bone formation and bone resorption, suggesting that the net result of PTH therapy may be either bone gain or bone loss depending on the dosage, mode of administration, bone site, and animal species. Histological studies established that intermittent PTH therapy was associated with an increase in trabecular bone and, importantly, with improvements in trabecular and cortical microarchitectural parameters that have not been reported with antiresorptive drugs. This anabolic effect of intermittent PTH therapy translates into increased biomechanical strength, despite the increase in endocortical porosity seen in humans and nonhuman primates. The biochemical response profile to intermittent PTH therapy in clinical trials indicated a phase of isolated anabolism followed by an overall increase in bone remodeling that predominantly affected bone formation, the result being a large increase in spinal bone mineral density as early as the first treatment year. Thus, intermittent PTH therapy exerts predominantly anabolic effects on bone.