Chromatin is dynamically changing its structure to accommodate and control DNA-dependent processes inside of eukaryotic cells. These changes are necessarily linked to changes of DNA topology, which might itself serve as a regulatory signal to be detected by proteins. Thus, DNA Topoisomerases may contribute to the regulation of many events occurring during the transcription cycle. In this review we will focus on DNA Topoisomerase functions in transcription, with particular emphasis on the multiplicity of tasks beyond their widely appreciated role in solving topological problems associated with transcription elongation.