Cumulative evidence indicates that the proteasome, which is mainly known as a protein-degrading machine, is very essential for gene expression. Destructive functions of the proteasome, i.e., ubiquitin-dependent proteolytic activity, are significant for activator localization, activator destruction, co-activator/repressor destruction and PIC disassembly. Non-proteolytic functions of the proteasome are important for recruitment of activators and co-activators to promoters, ubiquitin-dependent histone modification, transcription elongation and possibly maturation of mRNA via the facilitation of mRNA export from the nucleus to the cytoplasm. In this review, we discuss how the proteasome regulates transcription at numerous stages during gene expression. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough! (C) 2010 Elsevier B.V. All rights reserved.