Radiation therapy and chemotherapy for malignant tumors in the head and neck region are inevitably associated with injury to oral tissues, including the salivary glands. This often results in salivary gland hypofunction. Until now there has been no effective method of preventing damage caused by cancer therapies. Although not yet supported by sufficient evidence, there are some clinical trials indicating a potential benefit from radical scavengers and saliva stimulants. Other developments are in gene transfer to regain salivary gland function and stem cell transplantation to regenerate a diseased salivary gland. While irradiation on salivary gland tissue is irreversible to a large extent, hyposalivation associated with chemotherapy is usually less severe and reversible. In case of significant residual secretory capacity, supportive care is indicated. These patients are advised to stimulate their salivary glands by mechanical or gustatory stimuli. Alternatively, salivary flow can be stimulated by cholinergic stimulation (eg, pilocarpine or cevimeline). In the case of little or no residual capacity, palliative treatment is the only option. In such patients, nocturnal oral dryness can be alleviated by spraying oral surfaces with water or by applying a saliva substitute, particularly a substitute with gellike properties. During the day, the application of mouthwashes and saliva substitutes is indicated if moistening of oral surfaces with water is not sufficient. Recent developments are focusing on bioactive saliva substitutes and mouthwashes containing antimicrobial peptides to protect oral tissues against microbial colonization and to suppress or cure mucosal and gingival inflammation.