Many mental disorders and neurodegenerative and neurodevelopmental diseases involve cognitive deficits. Remarkable advances and new technologies are providing a clearer picture of the molecular basis of cognition. In conjunction with an SFN2010 symposium, we provided here a brief overview of the molecular mechanisms of cognition, with emphasis on the development of treatments for cognitive disorders. Activity-dependent changes in gene expression and protein synthesis integrate with synapse selection to form memory circuits. A neuronal activity-dependent molecular tagging system that uses the gene expression program to record memory circuit formation represents one new tool to study cognition. Regulation of protein translation, protein degradation, cytoskeletal dynamics, extracellular matrix interactions, second messenger signaling, and neurotransmitter receptor trafficking and function are all components of synaptic remodeling essential for cognition. Selective targeting of specific effectors in these processes, such as NMDA receptors, may serve as an effective strategy to treat cognitive deficits.