As outlined by Saba et al, the identification of EGFR as a biologically relevant cancer target, and the development of multiple high-specificity inhibitors of this target is unquestionably a great success story for the field of molecularly targeted therapeutics. These agents offer a clear and meaningful survival benefit to patients with cancers of the lung, head and neck, and colon. Compared with traditional cytotoxics, these targeted agents, as advertised, also offer less toxic therapeutic options. The flip side of the advertisement - that molecularly targeted therapy will offer highly refined individualized therapy - has not yet been fulfilled. Ongoing work by multiple groups, including analyses of genetic and epigenetic factors, gene-expression profiles, and proteomic profiles of tumor and patient serum, may help to further guide the administration of targeted therapy.