The epidermal growth factor receptor (EGFR)-mediated pathway is one of the most promising targets for the development of new strategies in anticancer treatments. The so-called "small molecule" tyrosine kinase inhibitor erlotinib has gained marketing authorization in the United States for advanced adenocarcinoma of the lung and for pancreatic cancer, whereas the antibody cetuximab is registered for metastatic colorectal cancer and cancers of the head and neck. Ongoing studies are evaluating the impact of EGFR-targeting therapy in the treatment of locally advanced and metastatic pancreatic cancer.