Proteomic and genomic technologies, particularly when combined as functional genomics, are promising experimental approaches to creating expression profiles of proteins and their connection to disease specific changes, starting with transcription and ending at the level of posttranslational modifications. It seems that molecular mechanisms underlying many neurodegenerative disorders may have common features. In a short amount of time, proteomics underwent unprecedented development from its early stages of collecting high numbers of protein identifications in a single experiment. Quantitative mass spectrometry of proteins is now a standard approach in all laboratories. However, analytical techniques based on principles of liquid chromatography are dominating and advancing the field. Further technological developments such as single cell analysis, will further facilitate a more precise view of changes occurring in proteomes resulting from alterations in biological systems. Another big step will be to go beyond slowing down or stopping neurodegenerative processes, and push the immune system to repair damage and promote regeneration. To what extent this is possible and how soon it can be accomplished remains an open question. It is certain, however, that understanding functions of complex biological systems, such as duality of neurotoxic/neurothrophic function of mononuclear phagocytes in the brain during inflammation, will require coordinated monitoring of a large number of parameters simultaneously and well-designed proteomic, genomic, and neuro-imaging experiments.