: The authors addressed the role and the management of pain in Paget's disease by a retrospective study. The objectives were: to assess the presence of pain in Paget's disease; to look for a relationship between pain and the levels of total alkaline phosphatase (total ALP); to verify if the most commonly used drugs in Paget's disease, calcitonin and bisphosphonates, were able to reduce the pain and the levels of total ALP. The study analyzed 107 Italian patients with Paget's disease who were hospitalized at the same Institute between 1970 and 2010; all patients affected by severe arthritis were excluded. From the analysis of the clinical records it emerged that as many as 85% of patients had pain and that total ALP was also increased in most of the patients with pain in comparison with patients without pain. The clinical and metabolic effects of different therapies were then assessed: many patients had not received any specific therapy (58%), others had been treated with calcitonin (25%) and others with bisphosphonates (17%). In fact, the patients treated with bisphosphonates had significantly lower levels both of pain and total ALP. The authors hypothesize that the pain in Paget's disease has a primary origin and is correlated to the degree of bone metabolic hyperactivity. Finally, treatment with bisphosphonates appeared to be the most appropriate treatment, having been able to control both the pain and the metabolic hyperactivity.