Electrical stimulation (ES) of the thalamic centromedian nucleus (CMN) has been proposed as a minimally invasive alternative for the treatment of difficult-to-control seizures of multifocal origin and seizures that are generalized from the onset. ES intends to interfere with seizure propagation in a non-specific manner through the thalamic system. By adopting a frontal parasagittal approach and based on anterior-posterior (AC-PC) commissure intersection, deep brain stimulation (DBS) electrodes are stereotactically inserted. Electrophysiologic confirmation of electrodes position is accomplished by eliciting cortical recruiting responses and direct current (DC) shifts by low- and high-frequency stimulation through the electrodes. Cycling mode of bipolar stimulation has been used at 60-130 Hz, 0.45 msec, 2.5-3.5 V, 1 min ON in one side 4 min OFF, 1 min ON in the other side and 4 min OFF forward and back for 24h. ES of CMN significantly decreases generalized seizures of cortical origin and focal motor seizures. Best results are obtained in non-focal generalized tonic clonic seizures and atypical absences of the Lennox-Gastaut syndrome. Experience has indicated that the most effective target for seizure control is the thalamic parvocellular centromedian subnucleus.