In Alzheimer's disease (AD) brain oxidative stress is observed indexed by several markers, among which are protein carbonyls and 3-nitrotyrosine, markers for protein oxidation. We hypothesized that identity of these oxidatively modified proteins would lead to greater understanding of some of the potential molecular mechanisms involved in neurodegeneration in this dementing disorder. Proteomics is an emerging method for identification of proteins, and its application to neurodegenerative disorders, especially AD, is just beginning. Posttranslational modification of brain proteins, particularly that due of oxidation of proteins, provides an effective means of screening a subset of proteins within the brain proteome that likely reflects the extensive oxidative stress under which the AD brain exists, and this new methodology provides insights into mechanisms of neurodegeneration in and new therapeutic targets for AD. In this review, the use of proteomics to identify specifically oxidized proteins in AD brain is presented, from which new insights into mechanisms of neurodegeneration and synapse loss in this dementing disorder that is associated with oxidative stress have emerged.