Sjögren's syndrome is a chronic, systemic, autoimmune inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, most notably the salivary and lacrimal glands. It results in loss of functional epithelium, diminished exocrine function, and gradual onset of dryness of the eyes, mouth, and other body parts (sicca syndrome). Because most patients with Sjögren's syndrome are female, this syndrome also represents a major women's health problem that is often misdiagnosed and undertreated. In this article, Drs Derk and Vivino review the criteria for diagnosis, common signs and symptoms, and strategies for increasing patient comfort.