This review describes the new research developments that have established the CNS-activity of some natural flavonoids. The properties of flavone, chrysin, apigenin and cirsiliol are described and a survey of the occurrence of ligands for the benzodiazepine binding site in the flavonoid field is attempted. Natural compounds, structurally related to flavonoids and with similar CNS-activities, are also included. A medicinal chemistry approach to improve the biochemical and pharmacological properties of the flavone nucleus is described alongside with the enumeration of the principal achievements obtained to date. Quantitative structure-activity relationships studies leading to the formulation of pharmacophore models presumably describing the characteristics of the flavone-binding site in the GABA(A)-receptor are summarized.