This article reviews current research on medication-overuse headache (MOH), and provides clinical suggestions for effective treatment programs. Epidemiological research has identified reliance on analgesics as a predictive factor in headache chronicity. MOH can be distinguished as simple (Type I) or complex (Type II). Simple cases involve relatively short-term drug overuse, relatively modest amounts of overused medications, minimal psychiatric contribution, and no history of relapse after drug withdrawal. In contrast, complex cases often present with multiple psychiatric comorbidities and a history of relapse. Although limited, current research suggests that comorbid psychiatric disorders are more prevalent in MOH than in control headache conditions, and may precede the onset of MOH. There appears to be an elevated risk of family history of substance use disorders in MOH patients, and an increased risk of MOH in patients with diagnosed personality disorders. Current studies suggest a high rate of relapse at 3 to 4 years after drug withdrawal and pharmacological treatment, with most relapse occurring during the first year of treatment. Relapse is a greater problem with analgesics than ergots or triptans. The addition of behavioral treatment to prophylactic medication may significantly reduce the risk of relapse over a period of several years. Clinical recommendations include assessment and modification of psychological factors that may underlie MOH, provision of detailed educational information, and combining behavioral treatment with the current standard of drug withdrawal and use of prophylactic pharmacotherapy.