Bisphosphonates belong to a class of compounds similar to pyrophosphate. In these compounds the oxygen atom of the pyrophosphate is replaced by a carbon atom resulting in a P-C-P bond. They exert a potent inhibitory effect on osteoclasts and are therefore potent antiresorptive agents. They reduce bone turnover, increase bone mineral density, and decrease fracture risk both at the lumbar spine and the hip. Bisphosphonates have a high affinity for bone surfaces, where they accumulate, mainly at sites of bone remodeling. Due to their selectivity in action, they are usually not associated with systemic side effects. Their main unwanted effect is upper gastrointestinal irritation. Alendronate and risedronate are the two most widely used compounds in the treatment of postmenopausal osteoporosis. They are administered orally either daily or once weekly. Ibandronate is a highly potent newer third-generation bisphosphonate administered once monthly with similar efficacy with respect to bone mineral density and fracture risk. Zoledronate, another potent third-generation bisphosphonate, currently approved for the treatment of malignancy-associated hypercalcemia, is currently undergoing phase III trials for the treatment of postmenopausal osteoporosis as an intravenous (i.v.) infusion once annually.