The transcription process is divided into three phases: Initiation, elongation, and termination. In prokaryotes, a single RNA polymerase carries out the transcription of all genes. There are three RNA polymerases in eukaryotes: pol I, II, and III. Each transcribes a distinct class of genes. The protein-coding genes are transcribed by pol II, which is the focus of our present book. In most cases, RNA polymerase holoenzyme initially binds to the promoter DNA in duplex form. The loading of the promoter DNA initiates a complex series of conformational changes resulting in a complex with two separated strands of approximately 12 base pairs, called the open-complex. The open-complex starts the RNA syntheses through nucleotide additions to an initiating nucleotide. In bacteria, the promoter is recognized directly by the sigma factors present in the holoenzyme. In eukaryotes, the open-complex formation requires assistance from several protein factors called general transcription factors. Archaea follow a pattern similar to eukaryotes but require a smaller number of general transcription factors. Once the RNA synthesis starts and reaches a certain length, the RNA polymerase escapes the promoter and enters the elongation phase. The elongation is highly processive but interrupted by many sequences that promote pauses. Continuous elongation needs assistance from elongation factors to overcome pauses. In eukaryotes, nucleosomes form barriers to productive and continuous elongation. Eukaryotes have evolved highly intricate machinery to overcome the nucleosomal barriers to smooth transcription. Once the polymerase reaches the end of the transcribed gene, the termination occurs in a manner that could be either a DNA sequence or external factor dependent. In this chapter, we have described the principal mechanisms of transcription initiation, elongation, and termination in all three domains of life.