Summary γ-Aminobutyric acid (GABA) mediates both fast synaptic inhibition and a tonic form of signaling that depends on high-affinity, extrasynaptic GABAA receptors. Tonic inhibition may contribute to the generation of spike-wave discharges. Because they have a profound effect on circuit excitability, tonically active GABAA receptors represent an important therapeutic target. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).