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 rho1, rho2 and rho3 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.