Sjögren's syndrome (SS) is a rheumatic disease in which the salivary and lacrimal glands are the principal targets of a pathologic autoimmune reaction. SS is manifested by xerostemia and keratoconjunctivitis sicca and marked by persistent focal mononuclear cell infiltration within the salivary glands, often accompanied by glandular atrophy and fibrosis. A challenge is to clarify the roles of genetic backgrounds and environmental trigger. Advanced bioanalytic platforms have enabled identification of potential biomarkers with the intent to improve diagnosis, promote development of prognostic tools, and identify processes for therapeutic treatment. Such approaches allow a glimpse at the apparent complexity of SS.