Sjögren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine glands and is a major cause of dry eye and is characterized by involvement of the lacrimal and salivary glands, resulting in chronic dryness of the eyes and mouth from decreased secretory functions. Etiology of the disease is not established but appears to be multifactorial. Dry eye, the principal ocular manifestation of SS results from decreased tear production or increased evaporative loss; Pathological changes observed in the lacrimal glands include increased cell apoptosis, infiltration by lymphocytes, and reduced transit of water across the lacrimal gland. Diagnosis, ocular and extra ocular manifestations and management of SS are discussed in the chapter. Anti-inflammatory agents, topical cyclosporine are used to treat SS patients.