The structure of the GABAA receptor, through which GABA--the main inhibitory neurotransmitter in the mammalian CNS--produces its major synaptic effects, has recently been identified. The GABAA receptor is a member of a family of receptor-operated ion channels to which the nicotinic cholinergic receptor-cation channel and the glycine receptor-anion channel belong. The GABAA receptor, formed by two different subunits with structural homologies, contains at least two pharmacologically important allosteric modulatory sites, one being the BZR. The BZR responds to two classes of active ligands, namely the so-called BZR agonists, which produce a positive modulation of GABAA receptor function resulting in anxiolytic, anticonvulsive, sedative, and muscle relaxant activity, and the so-called BZR inverse agonists, which produce a negative allosteric modulation of the GABAA receptor function resulting in a mirror image of the agonist profile. The effects of these two extreme classes of ligands (with maximal positive and negative intrinsic efficacy, respectively) are blocked by BZR antagonists, ligands of the BZR devoid of relevant intrinsic efficacy. Flumazenil is the first BZR antagonist available for therapeutic use. The molecular basis of the activities of BZR ligands and of their interactions has enormously increased our understanding of the complex function of neuronal receptors and neurotransmitters.