GABA A receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABA A receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fine-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABA A receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent findings highlighting the significance of GABA A receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifically, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABA A receptors, for controlling neuronal excitability; (2) significance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABA A receptor regulation (trafficking, posttranslational modification, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these findings is discussed in light of the involvement of GABA A receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identification of mutations in GABA A receptor subunit genes underlying familial forms of epilepsy.