Colorectal cancer remains a leading cause of cancer deaths. Over the last decade, many new drugs have emerged in the treatment of metastatic colorectal cancers. Thus, significant progress has been achieved with daily use of oxaliplatin, irinotecan, or similar oral 5-fluorouracil (capecitabine or UFT). The identification of new molecular targets has allowed the development of new antitumor agents directed against receptors for growth factor or cons key factors involved in the process of angiogenesis. Large randomized trials of metastatic colorectal cancer have demonstrated significant clinical benefit with bevacizumab (inhibiting the vascular endothelial growth factor VEGF) and inhibitors of epidermal growth factor receptor (EGFR), namely cetuximab and the panitumumab. In this article, we review the role and impact of mutational status of KRAS in the care of patients with colorectal cancer metastasis.