This review will provide an overview of therapeutic strategies that are targeted to the epidermal growth factor receptor (EGFR) network of signal transduction, with a focus on EGFR itself and the closely related Her-2/neu/ erbB2 (erbB2) receptor. EGFR is the founding member of the erbB family of receptor tyrosine kinases, type I membrane spanning proteins that bind a variety of peptide growth factor ligands and initiate signal transduction along multiple downstream pathways towards proliferation, survival and angiogenesis. EGFR and erbB2 are validated targets for anticancer therapy and several such targeted therapeutic agents are already approved for use in patients. These include monoclonal antibodies directed to the extracellular domains of one or more erbB receptor and small molecule inhibitors of their intracellular tyrosine kinase domains. The advantages and disadvantages of these agents, as well as new and emerging agents in this class of targeted therapeutics, will be discussed. Recent progress towards understanding the molecular and pharmacodynamic causes of treatment failure or success will also be addressed. Finally, the therapeutic potential of targeted combinations, those directed at multiple facets of erbB-family signalling and those targeted to erbB and non-erbB receptor systems, will be reviewed.