Mass spectrometry has been widely used in the field of diabetes. The development of new ionization methods and the effective coupling of mass spectrometry with liquid chromatography have enabled the protein modifications due to glycation processes to be investigated. Matrix assisted laser desorption/ionization mass spectrometry (MALDI/MS) has been used to evaluate the degree of glycation of specific plasma proteins. In contrast, the classic proteomic approach has been used to identify glycation sites and condensed sugar modifications. The same methods have been applied to studies on urinary protein profiles, enabling changes due to the development of long-term, diabetes-induced nephropathy to be identified. Published studies demonstrate that mass spectrometry is an important analytical tool for monitoring diabetes, capable of providing physicians with a new, more complete view of the physiopathological changes occurring as the disease develops.