Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise 5-fluorouracil (5-FU), folinic acid and irinotecan or oxaliplatin. Infusional 5-FU, folinic acid plus oxaliplatin (FOLFOX) is a standard of care not only for patients with stage IV disease, but also in the adjuvant setting of stage III colon cancer patients. The EGF receptor antibody, cetuximab, induces synergistic antitumor activity when combined with chemotherapy. In pretreated patients, cetuximab may restore the sensitivity to irinotecan and, therefore, has been registered in this setting. A number of Phase I and II trials investigated the combination of cetuximab plus oxaliplatin-based chemotherapy for the first-line treatment of mCRC. This combined cytotoxic and targeted treatment approach prooved to be safe and provided encouraging efficacy data, which are among the highest so far observed in the systemic treatment of mCRC. This review presents recent data on oxaliplatin, cetuximab and the combination of both for mCRC as well as possible future indications in the palliative, adjuvant and neoadjuvant setting of modern CRC treatment.