One of the more notable observations made in the last few years in gene regulation is that eukaryotic genomes appear to be pervasively transcribed. Recent transcriptome mapping studies have shown that much of the genome is transcribed, and in some instances transcripts from both strands of specific genomic loci are detectable. While some of these transcripts map to known RNA polymerase II transcription units [that is, protein encoding open reading frames (ORFs)], many are derived from regions of DNA thought to be non-genic. Parallel chromatin immunoprecipitation studies of template-bound RNA polymerase II have shown that it is indeed resident on those regions found to be transcribed, both ORF and non-ORF. However, the strandedness of these pervasive transcripts has never been measured on a genome-wide basis. Four recent reports have addressed this question and, in the process, have made the startling discovery that many loci of mRNA sense gene transcription are associated with very active antisense or divergent transcription that begins at mapped transcription start sites and proceeds in an upstream direction.