Patients suffering from frequent migraine attacks or chronic tension-type headache are at risk of developing drug-induced headache (now called 'medication overuse headache' [MOH]) as described by the new classification of the International Headache Society. This headache entity is caused by frequent use of antiheadache compounds (non-opioid analgesics, ergot alkaloids, 5-HT agonists, combined preparations with caffeine or codeine) for more than 15 days/month. Most patients, however, use the medication daily. The standard therapy of MOH is withdrawal therapy (mostly under in-patient conditions) followed by prophylactic treatment of the primary headache. The relapse rate reaches up to 40% within 1 year after a previously successful withdrawal therapy. The pathophysiology of MOH remains to be determined and, consequently, therapy has been driven by experience rather than by scientific hypotheses. The identification of predictors for both medication overuse and relapse after successful withdrawal should improve prevention and therapy in the future. Several medical (e.g., class of overused drugs) and psychological (e.g., standard of performance) predictors were recently identified. Medication overuse in headache patients is based on multiple factors with physical, social and psychological impact. In view of the high prevalence and relapse rate, it is necessary to establish a structured post-treatment programme for patients after the acute withdrawal phase, which considers the predictors for relapse.