**Abstract**

The treatment for patients with metastatic colorectal cancer has progressively improved over the past few decades with the development of more effective anticancer drugs and multi-disciplinary management approaches that combine sequential lines of non-cross-resistant drugs and increased use of potentially curative surgery for metastases of the liver and lung. In this setting, the introduction of monoclonal antibody therapies that target the epidermal growth factor receptor (EGFR) (cetuximab and panitumumab) has made an important contribution to improved patient outcomes. However, the efficacy of therapies is generally limited to a small proportion of patients and associated with toxicity and high cost. There is an urgent clinical need for robust predictive biomarkers to guide the effective use of therapy options. In this chapter we review clinical and molecular predictive markers of primary therapy response for metastatic colorectal cancer, focusing on anti-EGFR antibody therapies, discussing both currently approved and emerging biomarkers.

**Keywords:** metastatic colorectal cancer, epidermal growth factor receptor (EGFR), cetuximab, panitumumab, predictive biomarkers
