Autoimmune disorders, medical interventions, and aging are all known to be associated with salivary gland hypofunction, which results in the uncomfortable feeling of dry mouth (xerostomia) and significantly diminished oral health. The current therapeutic regimen includes increasing oral hydration using over-the-counter oral comfort agents and the use of systemic cholinergic drugs to stimulate salivary output. However, these approaches produce very transient relief or are associated with uncomfortable side-effects. Thus, new treatments that provide long-lasting relief from discomfort and improve oral health with minimal side-effects would benefit the therapy of this disease. The processes that mediate fluid loss from the oral cavity, such as the absorption of fluid from the oral mucosa, represent novel therapeutic targets for xerostomia. Preventing fluid absorption from the oral cavity is predicted to improve oral hydration and alleviate the clinical symptoms and discomfort associated with dry mouth. Furthermore, therapeutic strategies that prevent fluid absorption should complement current approaches that increase salivary output. This review discusses the current understanding of oral fluid balance and how these processes may be manipulated to provide relief for those suffering from dry mouth.