We now get benefit from more than 20 antiepileptic drugs (AEDs) in the care of people with epilepsy. Newer generation of AED is associated with a more favourable tolerability profile than older generation AEDs which makes them easier to use, despite similar efficacy. In order to define the place of newer generation AEDs in the therapy, we review here the main current guidelines about their use for a special issue concerning antiepileptic drugs in neurosurgical practice. We also discuss how to tailor the treatment with newer generation AEDs according to the patient’s needs and comorbid conditions. We review different common setting that may require specific therapeutic considerations, i.e. elderly, pregnancy, HIV infection, tumours and hospital/critical care use. We also discuss the current evidence regarding the use of newer generation AEDs in the neurosurgical practice. We present the most recent commercially available newer AEDs (ezogabine, perampanel, brivacetam, everolimus), describing their mechanism of action, adverse effects and indication according to the type of seizure. We finally describe the promising AEDs that are currently under development or testing. This article is a special issue concerning antiepileptic drugs in neurosurgical practice.