Much of the mammalian genome is transcribed, generating long non-coding RNAs (lncRNAs) that can undergo post-transcriptional surveillance whereby only a subset of the non-coding transcripts is allowed to attain sufficient stability to persist in the cellular milieu and control various cellular functions. Paralleling protein turnover by the proteasome complex, lncRNAs are also likely to exist in a dynamic equilibrium that is maintained through constant monitoring by the RNA surveillance machinery. In this Review, we describe the RNA surveillance factors and discuss the vital role of lncRNA surveillance in orchestrating various biological processes, including the protection of genome integrity, maintenance of pluripotency of embryonic stem cells, antibodygene diversification, coordination of immune cell activation and regulation of heterochromatin formation. We also discuss examples of human diseases and developmental defects associated with the failure of RNA surveillance mechanisms, further highlighting the importance of lncRNA surveillance in maintaining cell and organism functions and health.Non-coding RNAs (ncRNAs) are a type of RNA that are not translated into protein and include small ncRNAs (such as microRNAs) in the range of 15-30 nucleotides 1-3 and long ncRNAs (lncRNAs), which are generally considered as longer than 200 nucleotides 4 . LncRNAs include a variety of transcripts, all of which can modulate gene expression in specific ways based on cell type, developmental stage and function 5-7 (Box 1). As only a fraction of lncRNAs may be biologically relevant to a given process, cells use RNA surveillance pathways to identify and degrade most lncRNAs.RNA surveillance is necessary for genome stability and gene expression [8][9][10] . Whereas mechanisms of mRNA surveillance have been extensively reviewed 11,12 , less is known about the surveillance of the diverse types of lncRNA. Although the various components of the RNA surveillance pathways are still being characterized, it is known that endoribonucleases, 5′-exoribonucleases and 3′-exoribonucleases can degrade nascent lncRNAs, often with the