Reactive oxygen species, generated as normal by-products of aerobic metabolism or due to cellular stress, oxidize molecules and cause cell death by apoptosis. The accumulation of oxidized proteins is a hallmark of aging and a number of aging diseases. Oxidation can impair protein function as the proteins are unfolded leading to an increase of protein hydrophobicity and often resulting in the formation of toxic aggregates. The yeast Saccharomyces cerevisiae has been used as a eukaryotic model system to analyze the molecular mechanisms of oxidative stress protection. This paper reviews how the identification in yeast of specific damaged proteins has provided new insights into mechanisms of cytotoxicity and highlights the role of repair and degradative processes, including vacuolar/lysosomal and proteasomal proteolysis, in housekeeping after protein oxidative damage.