Epilepsy is a group of chronic neurological diseases of the brain characterized by a persistent predisposition to epileptic seizures, affecting more than 70 million people worldwide. Drug-resistance is a key problem in the theory and practice of epileptology. The literature contains many publications devoted to ultrastructural changes in brain tissue in experimental animal models, but the features of ultrastructural changes in human brain tissue in drug-resistant mesial Temporal Lobe Epilepsy (TLE) remain unknown. This brief review presents the current state of the art of problems devoted to the study of the ultrastructure of neurons, glia, and blood vessels in patients with drug-resistant mesial TLE.