The transcription factor Elk-1, a nuclear target of Mitogen Activated Protein kinase (MAPK) signalling pathways, plays a pivotal role in immediate early gene induction by external stimuli on cell culture systems. Notably, the degree of phosphorylation of Elk-1 is tightly correlated with the level of transcriptional activation of c-fos by proliferative signals. We review here data concerning Elk-1 expression and regulation in the adult central nervous system (CNS). Notably, we show evidences of its cytoplasmic (including dendritic and somatic) as well as nuclear localization in neuronal cells. Furthermore, the activation of Elk-1 by MAPK of the Extracellular signal-regulated kinase (ERK) subfamily is one of the key event underlying immediate early gene regulation upon glutamate receptor stimulation. However, contrasting with cell line models, the activation of Elk-1 occurs in dendritic as well as somatic and nuclear compartments. Altogether, these data bring new insights in intracellular mechanisms underlying gene regulation and synaptic plasticity in the CNS.