In metastatic colorectal cancer disease progression correlates with serum VEGF levels. The importance of VEGF in tumor-induced angiogenesis is well described in preclinical models. In this review we discuss the role of anti-VEGF therapy in combination with oxaliplatin-based chemotherapy for the treatment of metastatic colorectal cancer. A recent Phase III clinical trial in patients with metastatic colorectal cancer demonstrated the efficacy of FOLFOX4 in combination with bevacizumab, a recombinant humanized monoclonal antibody with high binding specificity for VEGF, to improve median overall survival when used as second-line therapy. The major adverse events associated with bevacizumab include grade III hypertension, bleeding and the risk of gastrointestinal perforation. Combining bevacizumab with oxaliplatin-based chemotherapy as first-line treatment for patients with metastatic colorectal cancer improves progression-free survival, as seen in the NO16966 and Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) studies, when compared with placebo and historical controls, respectively. Future research will need to focus on the mechanisms whereby bevacizumab enhances the benefit of chemotherapy to identify predictive markers that better define which patient populations will benefit the most from treatment.