Ampakines are the first peripherally administered drugs that increase excitatory monosynaptic responses in the brain. Because of this effect, the compounds improve communication in complex networks, potently facilitate long-term potentiation (LTP) and induce the expression of neurotrophic factors. Ampakines are effective in animal models of neuropsychiatric disorders and have produced positive results in a small number of human studies. Neurobiological considerations and modeling studies suggest that the drugs, in addition to their effects on disturbed behavior, will alter the encoding and organization of information in normal brains. Results from physiological and behavioral studies accord with this prediction. Building on these findings, this article considers how the threefold effects of ampakines will modify, and enhance, cognition.