High-throughput experiments have produced convicing evidence for an extensive contribution of diverse classes of RNAs in the expression of genetic information. Instead of a simple arrangement of mostly protein-coding genes, the human tran- scriptome features a complex arrangement of overlapping transcripts, many of which do not code for proteins at all, while others “sample” exons from several different “genes”. The complexity of the transcriptome and the prevalence of non- coding transcripts forces us to reconsider both the concept of the “gene” itself and our understanding of the mechanisms that regulate “gene expression”.