The development of specific inhibitors of bone resorption has revolutionized the treatment of Paget's disease. The diphosphonates, the calcitonins, and mithramycin are capable of inducing marked suppression of disease activity for prolonged periods as judged by biochemical, kinetic, and histologic techniques. Whereas the effects of the calcitonins and mithramycin persist only for the duration of treatment, diphosphonate treatment consistently results in a reduction of disease activity for many months or even years after stopping treatment. The question arises whether the long-term control of the disease activity confers significant clinical advantages to the patient. Relief of bone pain, spinal neurologic syndromes, immobilization hypercalcemia, and high-output cardiac failure are related to the degree of biochemical control attained by treatment. New bone formed during treatment is lamellar and radiologic progression of disease is favorably modified. It is not yet known whether long-term treatment will decrease bone enlargement and deformity or reduce the risk of fracture.