Epilepsy is considered as drug-resistant when seizures persist despite the administration of 2 antiepileptic drugs adapted to the patient's needs, with an effective dosage, well-tolerated, whether as a single agent or in combination. Any patient suffering from drug-resistant focal epilepsy should be evaluated at least once in a tertiary epilepsy centre to discuss the appropriateness of a pre-surgical work-up. In drug-resistant epilepsy, the determinants of quality of life are multifactorial and not exclusively linked to the seizure frequency. Anticipating the side effects of treatments is a key element during management of polytherapy. Screening for psychiatric and cognitive comorbidities must be systematic.