Colorectal cancer (CRC) is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. The epidermal growth factor receptor (EGFR) is overexpressed in the 80% of colorectal cancer and correlate with a poor prognosis. Cetuximab (C225, Erbitux TM) is chimeric human-mouse G1 immunoglobulin that binds to the EGFR with a 10-fold higher affinity than the natural ligands TGF?? and EGF. Cetuximab is currently licensed worldwide for the treatment of irinotecan-refractory metastatic CRC disease. It is well tolerated and the major adverse event is skin rash which also correlates with clinical response to treatment. An extensive phase II and III program of evaluation of cetuximab activity and efficacy in different settings of metastatic CRC has been undertaken. This article will review the current knowledge on the role of cetuximab in the medical management of metastatic CRC.