The epidermal growth factor receptor (EGFR) plays an important role in tumorigenesis and tumor progression of colorectal cancer (CRC). As a result, the EGFR has evolved as a relevant target in the treatment of metastatic CRC. Cetuximab, a monoclonal antibody used to target the EGFR, were recently approved in Japan for use as single agents or in combination with other chemotherapy drugs in the treatment of metastatic CRC. Cetuximab has demonstrated the clinical activity and unique adverse event profiles. Predictive markers of efficacy, including development of skin rash and the absence of a K-ras mutation, have been evaluated in clinical studies to identify patients likely to respond to anti-EGFR monoclonal antibody therapy. This article reviews recent clinical studies of cetuximab in the management of metastatic CRC, predictive markers of their efficacy that lead towards treatment individualization, and common toxicities associated with their use.