Regulation of transcription is a critically important process that controls development, differentiation, and the maintenance of cellular homeostasis. Cells have evolved numerous mechanisms to keep gene transcription tightly in check, some of which involve the ubiquitin-proteasome system. In this chapter, we review evidence supporting the concept that ubiquitin and the proteasome not only control transcription, but provide the biochemical means to drive key steps in the transcription process forward.