Monoclonal antibodies against the epidermal growth factor receptor have proven efficacy as monotherapy and in combination with chemotherapy in patients with metastatic colorectal cancer (CRC; mCRC). Initial clinical trials in CRC used the human-murine chimeric monoclonal antibody cetuximab. Ongoing studies are being conducted to evaluate the efficacy and safety of the fully human anti-epidermal growth factor receptor monoclonal antibody panitumumab. The results of a phase III trial, which compared panitumumab as a single agent to best supportive care in patients with previously treated metastatic CRC, have recently been reported. Panitumumab therapy resulted in a 46% reduction in the risk of tumor progression and a partial response rate of 8%. Rash was reported in 90% of patients, with increased severity significantly correlated with improved median overall survival (OS). Further clinical studies are ongoing and planned to test panitumumab in combination with chemotherapy in first-line therapy of advanced-stage CRC and adjuvant treatment of colon cancer.