Oxidative stress causes protein damage in mammalian cells. Modified proteins will be recognized and eliminated by the proteasomal system before severe protein aggregates emerge. It has been demonstrated that the 20S “core” proteasome is sufficient for recognition and degradation of mildly oxidized proteins whereas ubiquitination and ATP dependent protein degradation through the 26S proteasome does not seem to be necessarily involved. Proteasomal molecules are located in the cell either bound to cellular and organelle membranes or free in the cytosol and in the nucleus. The nuclear proteasome is strongly activated by a poly-ADP ribose polymerase mediated formation of poly(ADP-ribose). Recent studies support the hypothesis that the 20S proteasome is resistant to oxidation whereas the 26S form of the proteasome and the ubiquitination machinery seems to be more easily affected under oxidative conditions.