The article gives basic information on proteasome- and ubiquitin-dependent system of pro- tein degradation. The ubiquitination process of proteins designated for proteasomal breakdown and ubiquitin involvement in extraproteasomal cellular events is discussed. The article explains the struc- ture of 20S, 26S and PA700 complexes, the role of immunoproteasomes in the immune response and proteasomal proteolysis independent of ubiquitination. Moreover, it gives the outline of proteasomal biogenesis and possible clinical application of proteasome inhibitors.