The convergence of regenerative medicine, organogenesis, and tissue engineering provides an ideal blueprint to repair damaged tissues. Accordingly, a range of therapeutic applications have emerged that hold great potential to regenerate branching organs, such as salivary glands. This unique saliva-secreting organ is required for proper oral health, lubrication, immunity, and food digestion but is very susceptible to damage. Injuries to the gland can occur through collateral damage during radiation treatment of head-and-neck cancers, autoimmune-related Sjögren syndrome, disease-related medications, and surgical resection. This review chapter focuses on fundamental cellular and molecular processes occurring during salivary gland ontogenesis and development. We cover the growth of the epithelial compartment, which is a major functional component of the gland, but also how surrounding niches such as mesenchymal, endothelial, and neuronal cells communicate and influence the formation of salivary glands and other branching organs. Finally, we highlight how this key information has created new regenerative approaches and how these impact upcoming clinical translation.