Paget's disease of bone is a localized progressive disease, characterized by increased bone remodeling, bone hypertrophy, and abnormal bone structure, leading to pain and deformity. Disease complications involve the bones, joints, and central nervous system. Short-term treatment objectives are to alleviate or suppress bone pain; the long-term aim is for the prevention of complications caused by the slow disease progression in affected bones. The lifetime risk of complications depends on life expectancy, location, and activity index of Paget's disease. The use of potent and safe new bisphosphonates (tiludronate, pamidronate, alendronate, risedronate, and others) represents a major advance for the management of the condition: these compounds permit normalization of the biochemical indices of remodeling, and clinical doses have lasting effects without disruption to bone mineralization. Bone histomorphometry has shown that bisphosphonates can restore normal bone structure and an optimal therapeutic strategy should be defined. Symptomatic patients (or asymptomatic patients at risk) should be treated, as well as any patient requiring orthopedic surgery. The optimum strategy for preventing complications is to treat as early as possible and to halt disease progression by normalizing the biochemical markers that reflect the increased bone remodeling. There is no consensus on the threshold values for retreatment. Few studies have evaluated the long-term effects of the inhibitors of osteoclastic resorption on the risk of complications. A recent 12 year, long-term follow-up of 41 cases of Paget's disease has shown that antipagetic therapy that did not normalize biochemical markers in 71% of patients did not prevent new complications in 62% of patients. These results suggest that an optimal regimen of treatment and retreatment should target normalization of biochemical markers of bone remodeling; the new bisphosphonates make this quite feasible in most patients.