Publisher Summary This chapter provides an overview of the mammalian ErbB signaling network that has vital roles in the development and homeostasis, and its components are frequent and important targets for deregulation leading to cancer and other diseases. The network comprises multiple polypeptide ligands belonging to the epidermal growth factor (EGF) superfamily, and four related type I receptor tyrosine kinases, ErbB 1-ErbB4, which initiates signal. The EGF superfamily includes members of the EGF and Neuregulin subfamilies. The EGF group includes six independent gene products: EGF, transforming growth factor-alpha (TGFα), amphiregulin (AR), heparin-binding EGF (HB-EGF), betacellulin (BTC), and epiregulin (EREG) transduction. An apparent seventh member, epigen, was recently described. Transforming growth factor alpha (TGFα) is the best studied member of the EGF family.