During salivary gland morphogenesis, the developing ducts and acini must hollow out to form lumina which will eventually allow the free passage and modification of saliva on its journey from acini to oral cavity. The molecular mechanisms that participate in the creation of this tubular structure are of great research interest. Histological studies show that lumen formation begins during the mid stages of branching morphogenesis. At this stage, apoptotic cells are detectable in the developing salivary ducts at sites where lumina are forming, suggesting that programmed cell death is instrumental in clearing the luminal space. The formation of cell-cell junctions between the epithelial cells lining the space is also an integral part of lumen formation, since these junctions form a barrier around the lumen and allow the surfaces of the lumen-lining cells to become specialized. This chapter will discuss the mechanisms involved in salivary gland lumen formation during development, and draw on the most recent research in this interesting field.