Colorectal cancer (CRC) is a major contributor to cancer morbidity and mortality worldwide. Recently, the clinical application of molecular targeting therapy brings hope for treatment of metastatic CRC (mCRC). Following the approval of bevacizumab as first- and second-line treatment of mCRC, the therapeutic agents targeting vascular endothelial growth factor (VEGF) have been emerging constantly, and also shown significant efficacy in clinical trials. In this paper, the authors address the progress in VEGF-targeted therapy and the related biomarkers for mCRC.