Rapid degradation of specific proteins by ubiquitin/proteaseome-dependent pathways is a component of many cellular regulatory mechanisms. Recent work has shown that protein ubiquitination and deubiquitination are both mediated by large families of enzymes and that proteolysis can be modulated by alterations of the proteasome itself. The complexity of the ubiquitin system is reflected in the broad range of processes it regulates; these include key steps in cell cycle progression, processing of foreign proteins for presentation by class I MHC molecules, and the control of cell proliferation.