Despite the wide choice of antiepileptic drugs (AEDs), a third of patients remain resistant to the effects of modern AEDs. Drug-resistant epilepsy (DRE) is characterized by the inability to control seizures in a patient when using at least two adequate AED regimens at an effective daily dose as monotherapy or in combination. In this case, the mechanisms responsible for drug resistance are mainly either increased excretion of AEDs by transporters from epileptogenic tissue (the multidrug transporter hypothesis) or a decrease in the sensitivity of drug receptors in epileptogenic brain tissue. It is assumed that there are other mechanisms, but they remain understudied. A number of factors are associated with the risk of DRE developing in patients with diagnosed epilepsy, including genetic, iatrogenic, brain malformations, and others. Patients with DRE have a higher probability of developing psychopathological disorders (depression, anxiety, psychosis), the proportion of which is significantly higher than in the general population. They have a 10-fold increased risk of death due to injury, cognitive decline, and sudden unexpected death in epilepsy (SUDEP). The priority treatment method for DRE is surgery. Early identification of DRE is critical for identifying potential treatment alternatives and determining whether a patient is a surgical candidate. Analysis of data from clinical and instrumental research of operated patients with DRE in the early and late postoperative period will allow us to identify factors of unfavorable outcome and to increase the effectiveness of treatment for this category of patients. The aim was to study and to summarize literature data on the pathogenesis and risk factors of drug resistance to antiepileptic drugs in patients with epilepsy, justifying the need for timely identification of drug resistance and referral of patients with drugresistant epilepsy to specialized centers for possible surgical treatment.