Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjögren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent autoimmune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention.