Advances in recent mammalian large-scale full-length cDNA projects, have started to unravel the hidden features of the transcriptome. The majority of the genomic regions that were previously considered as a nonfunctional “transcript desert” are now reconsidered to be transcribed, producing multitudes of novel RNAs, including sense-antisense transcripts (SATs). SATs, which are transcribed from the same chromosomal location but in opposite directions, have been identified in various eukaryotic species. Surprisingly, SATs are recently reported to exist in several thousand gene pairs, but the biological meanings of these transcripts remain vague. In this article, we review the history and its currently proposed mechanisms of SATs, which has been collected from both individual and genome-wide research. In addition, we discuss the novel characteristics of SATs that have been revealed by current genome-wide expression analysis.