Current research exploring the molecular basis of memory focuses mainly on proteins despite recent genomic studies reporting the abundant transcription of non-protein-coding RNA (ncRNA). Although ncRNAs are involved in a diverse range of biological processes, they are particularly prevalent within the nervous system, where they contribute towards the complexity and function of the mammalian brain. In this review, we apply recent advances in ncRNA biology to predict a critical role for ncRNAs in the molecular mechanisms underlying memory formation and maintenance. We describe the role of ncRNAs in regulating the translation, stability, and editing of mRNA populations in response to synaptic activity during memory formation and the role of ncRNAs in the epigenetic and transcriptional programs that underlie long-term memory storage. We also consider ncRNAs acting as an additional avenue of communication between neurons by their intercellular trafficking. Taken together, the emerging evidence suggests a central role for ncRNAs in memory formation and provokes novel research directions in this field. NEUROSCIENTIST 14(5):434—445, 2008. DOI: 10.1177/1073858408319187