Members of the epidermal growth factor receptor family of receptor tyrosine kinases play a critical role in both development and oncogenesis. The latter is suggested by the frequent overexpression of HER-2, EGFR, and HER-3 in some human carcinomas, primarily breast and squamous cancer. The biological activities of the EGFR family are exerted through various ligand–receptor and receptor–receptor interactions. One receptor that plays a central role in this signaling network is HER-2/Neu, which is considered the preferred heterodimerization partner for other members of the EGFR family. The role of these receptors and their ligands in development is discussed, with particular emphasis on their ability to mediate a variety of pathways and cellular responses, including proliferation, differentiation, and apoptosis. © 2004 Wiley-Liss, Inc.