In recent years, the concept of an immunological background of some types of epilepsy has been gaining an increasing number of supporters. The following article is an attempt to review the most significant studies that explore irregularities in patients with intractable epilepsy, search for and identify the immunological causal factors of seizures and, finally, associate these factors with particular syndromes that manifest in refractory epilepsy. We also discuss the efficacy of immunomodulatory treatment in the recognized syndromes. Last, we focus on the immunological abnormalities found in patients undergoing antiepileptic therapy with classical antiepileptic drugs as well as changes in the immune system that could be provoked by an epileptic seizure itself.