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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. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (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.