In the last few years, a growing interest has arisen in the application of proteomic analysis to rheumatic disease. Sjögren's syndrome is a systemic disease that affects exocrine glands directly, and is therefore expected to influence the composition of the whole human saliva and lachrymal fluid. Therefore, a rising number of studies have been performed in an attempt to characterize the salivary and lachrymal protein profiles of patients with Sjögren's syndrome by using a proteomic approach. This review summarizes the state of the art and the potential application of proteomics in the systematic search for diagnostic biomarkers in Sjögren's syndrome.