The transcriptional regulation of the human EGFR3 and ERBB2 genes has been extensively studied, particularly in the context of their overexpression in breast cancer. Here we summarize published work detailing the transcription factors which interact with the promoters of these and the rat ERBB2 homologue, neu, genes and discuss their possible relevance to gene activation in cancer. In addition we review the biologically significant molecules which modulate expression of these genes and discuss the nuclear factors involved in mediating these responses. We also describe novel therapies which may result from these studies and highlight directions for future research into the control of expression of the EGFR and ERBB2 genes in the normal mammary gland and in breast cancer.