Abstract: Over the last few years, the development of large-scale technologies has radically modified our conception of genome-wide transcriptional control by unveiling an unexpected high complexity of the eukaryotic transcriptome. In organisms ranging from yeast to human, a considerable number of novel small RNA species have been discovered in regions that were previously thought to be incompatible with high levels of transcription. Intriguingly, these transcripts, which are rapidly targeted for degradation by the exosome, appear to be devoid of any coding potential and may be the consequence of unwanted transcription events. However, the notion that an important fraction of these RNAs represent by-products of regulatory transcription is progressively emerging. In this chapter, we discuss the recent advances made in our understanding of the shape of the eukaryotic transcriptome. We also focus on the molecular mechanisms that cells exploit to prevent cryptic transcripts from interfering with the expression of protein-coding genes. Finally, we summarize data obtained in different systems suggesting that such RNAs may play a critical role in the regulation of gene expression as well as the evolution of genomes.