GABA-C receptors belong to the nicotinicoid superfamily of ionotropic receptors that include nicotinic acetylcholine receptors, bicuculline-sensitive GABA-A receptors, strychnine-sensitive glycine receptors and 5HT3 serotonin receptors. The GABA-C receptor concept arose from medicinal chemical studies of a conformationally restricted analog of GABA. Receptors matching the predicted properties of GABA-C receptors were cloned from the retina. Post cloning studies revealed the unique physiology and pharmacology of these relatively simple homomeric receptors. Three subtypes of GABA-C receptors have been cloned from mammalian sources and pharmacological differences between the ρ1, ρ2 and ρ3 GABA-C receptors have been described. There is evidence for functional GABA-C receptors in the retina, spinal cord, superior colliculus, pituitary and the gut and their involvement in vision, aspects of memory and sleep-waking behaviour. This review concentrates on the medicinal chemistry and molecular pharmacology of GABA-C receptor subtypes emphasising possible new investigational tools with which to investigate further GABA-C receptor function. The most useful currently available ligands that show some GABA-C receptor subtype selectivity are TPMPA, P4PMA, imidazole-4-acetic acid, 2-methyl-TACA and (±)-TAMP.