Rapidly progressing proteomics techniques have been widely adopted in most areas of biology and medicine. In neurology and neuroscience, many applications of proteomics have involved neurotoxicology and neurometabolism, as well as in the determination of specific proteomic aspects of individual brain areas and body fluids in neurodegeneration. Investigation of brain protein groups in neurodegeneration, such as enzymes, cytoskeleton proteins, chaperones, synaptosomal proteins and antioxidant proteins, is in progress as phenotype related proteomics. The concomitant detection of several hundred proteins on a gel provides sufficiently comprehensive data to determine a pathophysiological protein network and its peripheral representatives. The rapid spread of proteomics technology, which principally consists of twodimensional gel electrophoresis (2-DE) with in-gel protein digestion of protein spots and identification by massspectrometry, has provided an explosive amount of results. An additional advantage is that hitherto unknown proteins have been identified as brain proteins. The current proteomics methods, however, have shortcomings and disadvantages. We would emphasize the failure to separate hydrophobic proteins as a major problem. So far, we have been unable to analyze the vast majority of these proteins in gels on 2-DE. There are several other analytical problems which also need to be overcome, and once solved, will allow for a more comprehensive analysis of the individual disease process. Here, we have reviewed the recent progress in proteomics research on neurodegeneration, with reference to its technological utility and problems in clinical application.