Activating mutations, gene amplification and overexpression of human epidermal growth factor receptor (erbB or HER) family kinases have been implicated as integral contributors to a variety of cancers. However, there is increasing evidence that the HER family receptors propagate not only signals initiated by their own ligands but also those initiated by multiple other signaling pathways. Attenuation of HER family signaling is a developing strategy for the management of human malignancies and is the subject of a number of ongoing clinical trials. The purpose of this review is to provide a timely update of recent reports in the rapidly evolving area of HER family biology and the emerging integral role of these receptors in malignant transformation and as targets of cancer therapy.