Complete seizure control is achieved in 40-50% of all epileptic patients with drug treatment, as reported in most epidemiological studies. Many effective antiepileptic drugs with a favourable profile are available in Switzerland, allowing treatment tailored to the patient's needs. Unfortunately, up to 40-50% of all patients will eventually relapse (pharmacoresistant epilepsy). These patients run a high risk of additional morbidity and mortality. Possible pharmacoresistant epilepsy should be considered early in the disease, when there is a lack of response to the first antiepileptic drug, since only 14% of those will respond to a second drug, and only 2% to a third drug if the second fails too. Epilepsy surgery is a viable option for these patients. It requires in-depth evaluation in specialized centres, and is related to complete seizure control in 50-90% of the patients, depending on the lesion type and site. Only for patients in whom surgery cannot be offered should neuromodulation treatments be considered. Today, two different approaches are approved, vagal nerve stimulation (VNS) and deep brain stimulation in the anterior thalamic nuclei (DBS-ANT). Although only a minority of patients become totally seizure-free. Both VNS and DBS-ANT represent an important adjunct in the therapeutic armamentarium. In the present review, we outline a practical approach for the different steps in therapeutic decisions and we summarise the profiles of modern antiepileptic drugs as well outcome of surgical and neuromodulatory therapies. The goal of any approach should be to obtain complete seizure control. In general, if two antiepileptic drugs are not successful, in-depth evaluation of the patient in a specialised center is strongly recommended.