Panitumumab is a fully humanized monoclonal antibody with a high degree of affinity for the extracellular domain of the epidermal growth factor receptor. Phase II clinical evaluation of this drug, when administered as a single agent, in patients with metastatic colorectal cancer refractory to chemotherapy, demonstrated a modest objective radiographic response rate with acceptable toxicity; the most frequently observed side effect is rash. A randomized phase III study in subjects with chemotherapy-refractory metastatic colorectal cancer documented a progression-free survival advantage in subjects treated with panitumumab plus best supportive care versus best supportive care alone; a difference in survival was not observed, likely due to the high cross over rate. Primary tumor KRAS mutation analysis performed in this study indicated that the benefit was confined to those patients whose tumors did not contain a KRAS mutation. Further studies with panitumumab will be required to develop biomarkers of response and to determine if panitumumab has a role in combination with cytotoxic chemotherapy. This article summarizes the current state-of-the-science knowledge on panitumumab therapy in the treatment of advanced colorectal cancer.