<p>This literature review presents data on the role of neuroinflammation with microglial and astrocytic dysfunction in the formation of elevated neuronal excitability and excitotoxicity, which in turn lead to increased seizure activity. The ability of reactive astrocytes to take up glutamate via specific transporters is reduced, resulting in increased cell excitability, excitotoxicity, and, consequently, the onset of epileptogenic activity. In general, neuroinflammation is associated with the activation of neuroplasticity processes, which can be maladaptive (aberrant) in nature. The processes of inflammation are also closely linked to activation of the sympathetic division of the autonomic nervous system, as evidenced by disturbances in the regulation of heart rate variability (HRV). Reduced HRV is closely associated with past infections and increased blood C-reactive protein and interleukin-6 concentrations. The interconnected processes of neuroinflammation, autonomic dysregulation, and aberrant neuroplasticity are important elements in the development of epilepsy, which must be taken into account when selecting optimal therapy.</p>