At every active gene in any genome, there is a transcription cycle, defined as the collective set of biochemical reactions that control RNA polymerase activity, from promoter binding to polymerase recycling. The transcription cycle serves as a command center where multiple sources of information are integrated to ensure that RNA synthesis across genomic loci is tailored precisely to the needs of the cell and organism. Despite its critical importance, our understanding of the transcription cycle is limited, and this lack of knowledge hampers our ability to manipulate transcriptional activity for myriad purposes, both in basic research and the applied sciences. Within this framework, in this issue of Transcription, we are excited to publish a series of reviews focused on key regulators of the transcription cycle: the transcriptional cyclindependent kinases or tCDKs. CDKs are a distinct class of serine-threonine protein kinases that share a core set of features, including the requirement of a cyclin partner and phosphorylation of their ‘activating T-loops’ by a CDK-activating kinase (CAK). In vertebrates, a distinct set of CDKs have clear roles in the regulation of cell cycle progression (CDK1,− 2,− 4,− 6), while a different subset is involved mostly in transcriptional control (tCDKs: CDK7,− 8,− 9,− 12,− 13,− 19)(ref 1–3). Our understanding of tCDKs has evolved rapidly in the last decade, yet for some of these proteins, our knowledge is still minimal, as in the cases of CDK12, CDK13, and CDK19. Even for the more well-studied tCDKs, such as CDK7 and CDK9, recent discoveries have changed our view of their mechanism of action and their roles in cell biology. Thus, we felt at Transcription that the time was right to have an updated view of the field, with a focus on recent discoveries and future venues for research. The need for these reviews is further justified by the increasing recognition that tCDKs could be valid targets of pharmacological intervention for the management of a number of human pathologies.