Under both physiological and pathophysiological conditions, responses mediated by GABA_A receptors are heavily influenced by (1) short-term changes in the anion gradients (chloride and bicarbonate) in postsynaptic neurons, and by (2) long-term changes in the expression of molecules involved in neuronal anion homeostasis. I will focus on our recent work on two molecules, the K-Cl cotransporter KCC2 and the cytosolic carbonic anhydrase isoform CAVII. The data obtained point to these molecules as key players in changes that take place in GABAergic inhibition under conditions related to the establishment and maintenance of epileptiform activity both in vitro and in vivo.