Recent evidence demonstrates that long non-coding RNAs (lncRNAs) regulate the expression of multiple genes in an epigenetic, transcriptional, or post-transcriptional manner. They are involved in various cellular phenomena, such as the recruitment of transcription factors, epigenetic chaperoning, control of alternative splicing, mRNA stability and translational activity, as well as acting as decoys against microRNAs. In this review, we summarize the pivotal roles of lncRNAs in regulation of the gene expression involved in neural cell differentiation, synaptogenesis and synaptic plasticity in the central nervous system (CNS). We also describe the aberrant expression of multiple lncRNAs involved in the pathogenesis of neurological diseases. The abnormal expression of lncRNAs leads to altered expression levels of target genes, which contributes to neurodegenerative diseases, such as in Alzheimer's disease and Parkinson's disease, and to the formation of tumors, such as glioma. Accordingly, we discuss recent findings for the modes of action of lncRNAs in normal CNS development and for aberrant lncRNA actions in the pathogenesis of neuronal diseases.