Abstract Absence epilepsy, a disease predominantly of childhood, has long been known to arise from an aberration of the interplay between two brain regions, the cortex and the thalamus. Pharmacological treatment of the disorder has advanced little during past decades, with ethosuximide and sodium valproate remaining the principle drugs of choice. Absence epilepsy is classified as a generalized seizure type and it has been widely assumed that the thalamus is the generator of this seizure activity. However, recent evidence has identified a specific site of seizure generation within the peri-oral region of the primary somatosensory cortex (S1po). Furthermore, ethosuximide has been shown to exert its inhibitory effect on absence seizure activity specifically at this focus, and not in other parts of the cortex or in the thalamus. A greater understanding of the molecular mechanisms within this cortical region might therefore give rise to newer, more effective treatments of absence epilepsy, and perhaps of other thalamocortical dysfunctions.