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Recent advancement in mass spectrometry leads us to a new era of proteomic analysis. Human saliva can be easily collected; however, the complexity of the salivary proteome in the past prevented the use of saliva for proteomic analysis. Here we review the development of proteomic analyses for human saliva and focus on the use of a new mass spectrometric technology known as surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). SELDI-TOF, a modification of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF), combines the precision of mass spectrometry and the high-through-put nature of protein arrays known as Protein Chips. This technology shows a promising future for salivary proteomic analysis in monitoring treatments and diseases, as well as novel biomarker discovery.