Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by complaints of sicca symptoms (dry eye and mouth) and can be associated with other autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, etc). As a result, SS can be difficult to diagnose. Currently, there are several criteria standards for SS, including the San Diego criteria and the European Study Group criteria. According to the San Diego criteria, the incidence of SS is about 0.5%, whereas for the European Study Group it ranges from 3% to 5%. This almost 10-fold difference in SS incidence has led to confusion for both the clinician and researcher. The tearing reflex involves a neural loop in which afferent nerve signals from the ocular surface are relayed centrally to the medulla. The input from the afferent nerves is then processed and sent back via efferent nerves stimulating blood vessels and secretory glands to provide and pump water for tears. Immune factors, such as cytokines, have a profound effect on the tearing mechanism by damaging secretory glands and releasing antibodies to influence the response of muscarinic M3 receptors. Thus, the interaction of neural and immune factors affects the secretory response of glands and contributes to the pathogenesis of SS sicca symptoms. The recent development of muscarinic agonists, such as pilocarpine and cevimeline, serves an important step in recognizing the interaction between the immune and neuroendocrine systems.