The function of mitogen-activated protein kinase (MAPK) in neurons has been the subject of considerable scrunity of late, and recent studies have given new insights into how this signalling cascade can regulate gene expression following cell-surface receptor activation. At the same time, a wealth of experimental data has demonstrated that the MAPK cascade is critically involved in the mechanisms underlying the type of enduring modification of neural networks required for the stability of memories, emphasizing the high level of interest in this signalling molecule. In this review, we briefly outline the main molecular events and mechanisms of the regulation of the MAPK cascade leading to transcriptional activation and summarize recent advances in our understanding of the functional role of this molecular signalling cascade in regulating brain plasticity, memory consolidation and memory reconsolidation.