AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors mediate fast excitatory transmission throughout the central nervous system. Positive modulation of these receptors can potentially enhance cognition by, firstly, offsetting losses of glutamatergic synapses; secondly, promoting synaptic plasticity; and thirdly, increasing the production of trophic factors. The advent of small molecules that selectively enhance AMPA receptors in the brain made it possible to test these hypotheses. Preclinical experiments indicate that the compounds accelerate the encoding of memory and have positive effects on models of cognitive dysfunction. Initial results with human subjects are also positive. AMPA receptor modulators thus represent an entirely new approach to cognitive enhancement and the treatment of diverse brain disorders.