The γ-aminobutyric acid type A (GABAA) receptors are the major inhibitory neuronal receptors in the mammalian brain. Their activation by GABA opens the intrinsic ion channel, enabling chloride flux into the cell with subsequent hyperpolarization. Several GABAA receptor subunit isoforms have been cloned, the major isoform containing α, β, and γ subunits, and a regional heterogeneity associated with distinct physiological effects has been suggested. As a variety of allosteric ligands can modulate GABA-gated conductance changes through binding to distinct sites, the development of subtype-selective ligands may lead to the selective treatment of GABA system- associated pathology. In particular, the best characterized binding site is the benzodiazepine site (BzR), localized at the α/γ subunit interface, in which the α subunit is the main determinant of BzR ligand action selectivity. The α1-containing BzR have been proposed to be responsible for the sedative action; the α2 and/or the α3 subtypes have been suggested to mediate the anxiolytic activity and the myorelaxation effects, and the α5 subtype has been associated with cognition processes. The discovery of α-selective subtype ligands may help in the specific treatment of anxiety, sleep disorders, convulsions and memory deficits with fewer side effects. Selectivity may be achieved by two approaches: selective affinity or selective efficacy. Selective affinity needs a compound to bind with a higher affinity to one receptor subtype compared with another, whereas subtype-selective efficacy relies on a compound binding to all subtypes, but having different efficacies at various subtypes. The status of BzR ligands, subdivided on the basis of their main chemical structural features, is reviewed in relation to structure-activity relationships which determine their affinity or efficacy selectivity for a certain BzR subtype.