Large portions of the genomes of higher eukaryotes are transcribed into RNA molecules that are never destined for translation into proteins. Although some of these transcripts have clearly defined biological roles other than protein coding, most arise from genomic regions devoid of functional genes and many are antisense to regions containing annotated genes. A variety of mechanisms exist to prevent adventitious production of proteins from these transcripts, ranging from degradation within the nucleus to translational silencing in the cytosol.