With the discovery of the involvement of the ErbB family of transmembrane growth factor receptors in tumour malignancy, major efforts have been undertaken to develop agents able to specifically target these receptors. With varying success, these agents have been applied to either detect the presence of ErbB receptors on cancer cells or to neutralize receptor function in order to put a hold on the unbridled tumour growth. The two most exploited classes of ErbB-targeting agents are monoclonal antibodies binding the extracellular portion of the receptor and small molecules able to interfere with the intracellular tyrosine kinase activity. Here we focus on the various kinds of agents that have recently been developed to target the extracellular region of the EGFR, the best characterised member of the ErbB family. Because clinical successes are relatively poor, alternative but less developed approaches for receptor targeting are being evaluated. Much effort has been put into the development of smaller antibody fragments. In this context, EGFR-binding nanobodies and affibodies may prove to be a more efficient novel approach in targeting EGFR-positive tumours for therapeutic and diagnostic use.