Protein-coding genes account for only a small fraction of the human genome and most of the genomic sequences are transcriptionally silent, but recent observations indicate significant functional elements, including non-coding protein transcripts in the human genome. Long non-coding RNAs (lncRNAs) have been defined as transcripts of >200 nucleotides without protein-coding capacity that perform their function through a number of mechanisms, including the recruitment of chromatin modifier complexes to specific genomic loci, the formation of molecular scaffolds, the modulation of transcriptional processes, and the regulation of miRNAs expression. Recent studies emphazied the increasing role of these lncRNAs in the pathogenesis of the different diseases, challenging the fact that protein-coding genes are the sole contributor to human disease. This study investigates lncRNAs and their crucial role in human diseases such as cancer, cardiovascular diseases, and multiple sclerosis.