The Epidermal Growth Factor family of peptide hormones and their four ERBB receptors are important in development of epithelia, the nervous system, and the cardiovascular system, and they continue to maintain these systems in adults. These growth factors and receptors are important drivers in human cancers, and they are the targets for several effective anti-cancer therapies in clinical use. The biology and pathogenesis of this system, and its importance for fundamental research in cancer biology is reviewed.