The complexity of a living organism is not driven by gene number but gene regulation. Controlling which genes to express and to what extent dictates the subsequent cell identity. Transcription, the critical initial stage in gene expression, is regulated delicately to maintain the cell status. Recent developments in the genomic approaches provided unparalleled coverage of the study of transcription. Still, basic molecular biology and biochemistry are providing mechanistic insights into how the regulation is achieved. In this feature “Regulation of transcription: mechanisms and biological functions”, the latest advances in epigenetics, mRNA processing, RNA quality control, and human immunodeficiency virus (HIV) transactivation are discussed.