Xerostomia is the subjective feeling of oral dryness. The major causes are Sjögren's syndrome (SS), medication and radiotherapy to the head and neck. SS is a chronic systemic autoimmune disease characterized by infiltration of the exocrine glands, the salivary and lacrimal ones in particular. The pathogenesis involves systemic B cell hyperactivity and T cell lymphocytes targeting glandular epithelial cells. About 7.5% of patients with SS develop malignant B cell lymphoma, mostly mucosa-associated tissue lymphomas. Certain classes of drugs can induce hyposalivation and/or xerostomia by, e.g., targeting neurotransmitters and receptors. As a result, amongst others the production of fluid and electrolytes in salivary glands can be reduced and the salivary composition can change. During head and neck radiotherapy, the administration of high doses to the major salivary glands, which are located in the periphery of the head, leads to progressive loss of glandular function and a diminished salivary output. Reduction of the dose and the volume of irradiated salivary glands by advanced radiotherapy techniques can be highly beneficial for patients.