Epilepsy is one of the main causes of functional disability, and it is usually associated to psychiatric comorbidity, such as psychosis of epilepsy (POE). POE requires more careful pharmacological treatment, considering the propensity of the antipsychotics (AP) to provoke seizures and the risk of pharmacokinetic interaction with anti-epileptic drugs (AEDs). We discussed the classification and the main types of POE, as well as some characteristics of AP typical and atypical, its potential to decrease the epileptogenic threshold (ET) and possible interactions between AP and AED. Atypical AP, except clozapine, disclosed smaller influence on ET than typical AP. Regarding pharmacokinetic interactions, AEDs are related with a significant increase of the AP metabolism. Therefore, in spite of the risk for AP induced convulsions be dose-dependent, higher doses of AP can be necessary in the treatment of POE.