Epidermal growth factor receptor (EGFR) is the best characterised member of the ErbB family of receptors. A lot of effort has been made to exploit the therapeutic potential of drugs acting on this receptor pathway. Monoclonal antibodies and oral tyrosine kinase inhibitors have undergone a thorough evaluation, both as single agents and in combination. However, over recent years, cancer cells have been shown to be able to harness different growth factor signalling pathways, so that single-agent therapy may not be the best way to use anti-EGFR drugs. Combinations with downstream effectors or other receptor-targeted therapies, or antiangiogenic compounds can be looked at more optimistically as effective weapons.