This mini-review describes recent discoveries demonstrating that experience can drive the production of epigenetic marks in the adult nervous system and that the experience-dependent regulation of epigenetic molecular mechanisms in the mature central nervous system participates in the control of gene transcription underlying the formation of long-term memories. In the mammalian experimental systems investigated thus far, epigenetic mechanisms have been linked to associative fear conditioning, extinction of learned fear, and hippocampus-dependent spatial memory formation. Intriguingly, in one experimental system epigenetic marks at the level of chromatin structure (histone acetylation) have been linked to the recovery of memories that had seemed to be “lost” (i.e., not available for recollection). Environmental enrichment has long been known to have positive effects on memory capacity, and recent studies have suggested that these effects are at least partly due to the recruitment of epigenetic mechanisms by environmental enrichment. Finally, an uncoupling of signal transduction pathways from the regulation of epigenetic mechanisms in the nucleus has been implicated in the closure of developmental critical periods. Taken together, these eclectic findings suggest a new perspective on experience-dependent dynamic regulation of epigenetic mechanisms in the adult nervous system and their relevance to biological psychiatry.