The salivary gland is a complex, secretory tissue that produces saliva and maintains oral homeostasis. Radiation induced salivary gland atrophy, manifested as “dry mouth” or xerostomia, poses a significant clinical challenge. Tissue engineering recently has emerged as an alternative, long-term treatment strategy for xerostomia. In this review, we summarize recent efforts towards the development of functional and implantable salivary glands utilizing designed polymeric substrates or synthetic matrices/scaffolds. Although the in vitro engineering of a complex implantable salivary gland is technically challenging, opportunities exist for multidisciplinary teams to assemble implantable and secretory tissue modules by combining stem/progenitor cells found in the adult glands with biomimetic and cell-instructive materials.