Investigational nitric oxide (NO) related therapeutic agents span the range from prodrugs that elevate NO levels, to scavengers of NO, and inhibitors of endogenous NO synthesis. The organic nitrate, nitroglycerin, has been used clinically in treatment of angina for 130 years, and more recently hybrid nitrates have entered clinical development for an increasing range of disease states. The therapeutic potential of pharmacological manipulation of NO is being explored in cardiovascular disorders, neurodegenerative disorders, cancer, and many other areas in which NO has a central biological role. Organic nitrates manifest NO mimetic activity in vivo; NO chimeras are NO mimetics that contain an ancillary pharmacophore. GT 094 is an NO chimera, possessing an anti-inflammatory pharmacophore, that shows promise in colon cancer chemoprevention. GT 1061 is an NO chimera that recently entered clinical trials for Alzheimer's disease. Many conditions adversely affecting learning, memory, and cognition are associated with reductions in forebrain acetylcholine, most notably aging and Alzheimer's disease. Bilateral depletion of neocortical and hippocampal acetylcholine in rats produces deficits in a spatial learning task and in a recently described delayed, visual matching-to-sample task. Oral administration of GT1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), and the acetylcholinesterase inhibitor, donepezil, reversed the cognitive deficits in both memory tasks in a dose-dependent manner. GT1061 was superior in the delayed matching-to-sample task. GT1061 was absorbed rapidly after oral administration, crossed the blood brain barrier, and achieved brain concentrations that were slightly higher than those found in plasma. The beneficial effect on visual and spatial memory task performance supports the concept that stimulating the NO/sGC/cGMP signal transduction system can provide new, effective treatments for cognitive disorders.