The first gerontological studies using two-dimensional gel electrophoresis (2DGE) were frustrating since it was very difficult, when not impossible, to identify the proteins for which an age-related change in expression level was suspected. Reproducibility was also a main pitfall. Accumulated progress in 2DGE and especially the development of mass spectrometry of proteins and peptides gave accessibility to the routine identification of differentially expressed proteins. A new paradigm was born: proteomics. In addition to expression changes, post-translational modifications are included in proteomics, and will be more and more studied using mass spectrometry. After a review of the current developments of 2DGE and mass spectrometry, we shall discuss how the technologies currently available in proteomics could give fresh impetus to experimental gerontology, complementary to more recent approaches based on wide expression analysis tools such as DNA and protein arrays.