Methods for protein analysis, such as chromatography, electrophoresis, enzyme tests, receptor assays and immunological tests, have always been aimed in a classical reductionistic manner at investigating single proteins isolated from the complex protein composition of biological compartments. The complexity of the protein composition in biological systems was first visualized by two-dimensional electrophoresis (2-DE). Using 2-DE like a molecular microscope, protein variations between different biological situations may be detected by subtractive 2-DE analyses. Combining 2-DE with microsequencing, amino acid analysis and mass spectrometry protein spots on 2-DE gels may be identified. The sequence information can be used to find the gene. However, by 2-DE not only single protein changes can be detected and investigated on the gene level, but also complex changes of many proteins on a genomic scale.