A balance between rapid, short lived, neuronal responses and prolonged ones fulfill the biochemical and cellular requirements for creating a molecular memory. I provide an overview of epigenetic mechanisms in the brain and discuss their impact on synaptic plasticity, cognitive functions, and discuss a recent example of how they can contribute to neurodegeneration and the cognitive decline associated with Alzheimer's disease. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.