Medication-overuse headache (MOH) has increasingly become a focus within the field of headache. The biologic and physiopathologic origin for MOH likely resides in receptor physiology, but it also is probable that the initiation and sustaining dynamics of this pathologic condition involve several other factors. Not all patients with frequent headache eventually overuse their medications, but when it happens (the percentage is approximately 1%), the diagnosis of MOH is clinically important because patients rarely respond to preventive medications while overusing acute medications. Properly treating medication overuse and preventing relapse require recognition of the different factors that contribute to its development and perpetuation, including some behaviors and psychologic elements that are important in sustaining the overuse of medication. The problem regarding the diagnosis, the classification, and clinical aspects of MOH is reviewed in this article. The different therapeutic approaches, initial outcomes, and long-term durability of treatment also are discussed.