AbstractMammalian salivary glands synthesize and secrete saliva via a vast interconnected network of epithelial tubes attached to secretory end units. The extensive morphogenesis required to establish this organ is dependent on interactions between multiple cell types (epithelial, mesenchymal, endothelial, and neuronal) and the engagement of a wide range of signaling pathways. Here we describe critical regulators of salivary gland development and discuss how mutations in these impact human organogenesis. In particular, we explore the genetic contribution of growth factor pathways, nerve‐derived factors and extracellular matrix molecules to salivary gland formation in mice and humans. WIREs Dev Biol 2015, 4:573–590. doi: 10.1002/wdev.194This article is categorized under: Signaling Pathways > Global Signaling Mechanisms Vertebrate Organogenesis > From a Tubular Primordium: Branched Birth Defects > Organ Anomalies