The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/NMDA receptor trafficking, neuromodulation (e.g., via dopamine, adrenaline, cortisol, or acetylcholine) and metabolic processes (e.g., via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By utilizing this information and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future. WIREs Syst Biol Med 2013, 5:37–53. doi: 10.1002/wsbm.1196

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Conflict of interest: C.M.A. has a patent on IGF-II as memory enhancer.