Chronic headaches and medication overuse headache are common and burdening conditions. No studies have evaluated the prevalence of chronic headache and medication overuse headache in an unselected Italian population. We performed a three-year cross-sectional and longitudinal population-based study to investigate prevalence, natural history, and prognostic factors of chronic headache. We delivered a self-administered questionnaire to 25,163 subjects. Chronic headache patients were interviewed by General Practitioners. After three years, medication overuse headache patients were invited to undergo a neurological evaluation at our Center. 16,577 individuals completed the questionnaire; 6878 (41,5%) were episodic headache sufferers and 636 (3.8%) were chronic headache subjects. 239 (1.4%) patients were acute medication over-users. All medication overuse headache patients had migraine or headache with migrainous features. At the three-year follow-up of 98 patients, we observed conversion to episodic headaches in 53 (54.1%) patients. 27 (50.9%) patients remitted spontaneously. We present the first prevalence data on chronic headache and medication overuse headache in an unselected Italian population and a high rate of spontaneous remission. These data support the interpretation of medication overuse headache as a specific migraine-related disorder that may reflect chronic migraine's dynamic nature, the need for more specific medication overuse headache diagnostic criteria, and highlight the priority of targeted public health policies.