Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) are effective in the treatment of metastatic colorectal cancer. Cetuximab is a human-murine chimeric monoclonal antibody targeting the EGFR. Even with premedication, cetuximab can result in an infusion reaction in select patients. In a portion of these patients, the reaction is severe, and further therapy with cetuximab is contraindicated, thus preventing these patients from receiving potentially beneficial anti-EGFR therapy. Panitumumab is a fully human monoclonal antibody also targeting the EGFR. Panitumumab is given without premedication and, in clinical trials, has rarely been associated with infusion reactions. It is not yet known whether panitumumab can be safely given in patients with a previous severe reaction to cetuximab. We report a case of a patient successfully treated with panitumumab after the patient had a severe infusion reaction to cetuximab.