GABA (γ-aminobutyric acid) is abundantly expressed within the brain, and spinal cord pain circuits where it acts as the principal mediator of fast inhibitory neurotransmission. However, drugs that target GABAA receptor function such as the classical benzodiazepines have not been optimised to promote analgesia, are limited by side effects and are not routinely used for this purpose in humans. Compounds such as NS11394, L-838,417, HZ166 and TPA023 all bind to the same benzodiazepine site on the GABAA receptor to allosterically modulate receptor function and enhance the actions of GABA. By virtue of their ability to activate selected subtypes of GABAA receptors (principally those containing α2, α3 and α5 subunits) these compounds have been shown to possess excellent tolerability profiles in animals. Importantly, a number of these molecules also mediate profound analgesia in animal models of inflammatory and neuropathic pain. Other modulators such as neurosteroids bind to distinct sites on GABAA receptor α subunits, possess a unique pharmacology and are capable of targeting alternative GABAA receptor expressing populations. Moreover, neurosteroids also have pronounced analgesic actions in animal pain models. The continuing call for novel mechanism of action analgesics to target specific pathologies, especially in clinical neuropathic conditions, emphasizes the need to test modulators of GABAA receptor function in both human experimental pain models and pain patients.