The epidermal growth factor receptor (EGFR) is widely expressed in advanced colorectal cancers (CRCs), and higher levels of EGFR are inversely related to survival in these patients. Two general strategies have been used to block EGFR signaling: preventing ligand binding with anti-EGFR monoclonal antibodies (eg, cetuximab and ABX-EGF) and inhibiting its intrinsic tyrosine kinase with small molecules (eg, gefitinib [Iressa] and erlotinib [OSI-774,Tarceva]). Phase II trials of cetuximab suggest that it might be an effective treatment option alone or in combination with standard therapies as first- or second-line therapy. Phase I studies evaluating other EGFR inhibitors in patients with CRC have been reported. The inclusion of anti-EGFR therapies into standard treatment is the subject of current clinical trials.