Relatively few effective therapies exist for the multitude of disorders that comprise dementia, a clinical syndrome manifested by impairments in cognition, language and memory. Treatment of Alzheimer s disease (AD), the most common cause of dementia, is a primary goal of research in cognitive enhancement. However, despite intense research, effective pharmacological interventions remain to be developed. The preponderance of pharmacological strategies which are being pursued in AD research attempt to relieve cognitive and memory deficits which are attributed to cholinergic dysfunction. This paper briefly reviews the status of other efforts that have in common the potential to enhance the use-dependent activity of multiple neurotransmitters system through the modulation of gated ion channels. Discussed are recent advances in the areas of: 1) g-aminobutyric acid subtype A receptor/benzodiazepine (GABAA/BZ) inverse agonists; 2) nicotinic acetylcholine receptor (nAChR) agonists; 3) serotonin subtype 3 receptor (5-HT3R) antagonists; and 4) potassium (K+) M-channel inhibitors.