This special issue aims to assemble available knowledge on long noncoding RNAs (lncRNAs) and provide future research directions for discovering the molecular functions of this emerging family of molecules. The genomes of eukaryotes, particularly mammalian species including human and mouse, possess large chunks of nonprotein-coding regions. Only 2% of the human genome is dedicated to coding for proteins; the remainder is constituted of noncoding regions, which are for the most part functionally unannotated. At the beginning of the postgenomic era, transcriptome genome-wide analyses in various organisms unexpectedly revealed that large portions of the mammalian genome produce numerous transcripts that lack protein-coding potential. Among these RNAs, noncoding transcripts longer than 200 nt are arbitrary referred to as “lncRNAs”. Many lncRNAs are expressed at low levels, exhibit tissue- or cell type specific expression patterns, and are not as well conserved between species as protein-coding mRNAs. LncRNAs share common features with protein-coding mRNAs; for instance, with few exceptions, they are transcribed by RNA polymerase II, possess the canonical cap structure at their 5′ termini, and their 3′ termini are polyadenylated. Nevertheless, many lncRNAs are not subject to nuclear export and function within the nucleus, which is in sharp contrast to mRNAs that are transported to the cytoplasm and translated into proteins. Notably, a group of lncRNAs, once classified as lncRNAs, have now been found to encode small polypeptides, making it necessary to establish new methods to distinguish lncRNAs from polypeptide-coding RNAs...