About 25% of all childhood epilepsies are difficult to treat. These patients do not become seizure free through antiepileptic medication, except if they accept side effects that constitute severe handicaps. Aside from general risk factors (age at onset, concomitant disability, etc.), the epilepsy syndrome and its aetiology are major predictors of whether or not the course will be complicated. Once treatment with two antiepileptic drugs thought to be appropriate and given in adequate doses has failed, diagnostic and therapeutic management must be closely coordinated. The epilepsy syndrome must first be re-evaluated by means of a detailed history anamnesis of the seizure semiology, neurological examination, and EEG and MRI examination. Early presurgical evaluation is indicated in the case if focal epilepsy with or without any lesion, and in patients with a potentially epileptogenic lesion regardless of the seizure semiology. Accurate diagnosis of the epilepsy syndrome is essential if in the next step the most promising treatment for an individual patient is to be selected from the many available.