Angiogenesis is now a proven therapeutic cancer target. Approaches targeting the vascular endothelial growth factor and receptor (VEGF/VEGFR) axis have yielded success in gastrointestinal cancers. Bevacizumab is a humanized recombinant monoclonal antibody against VEGF and is the first antiangiogenic drug to enter clinical practice. Bevacizumab was approved for the treatment of advanced colorectal cancer by US FDA in 2004 in combination with fluorouracilbased chemotherapy. Hepatocellular carcinoma (HCC) is the next gastrointestinal cancer where angiogenesis proved to be of therapeutic importance. Sorafenib is a multi-kinase inhibitor of VEGFRs and Raf protein, and demonstrated anticancer effects in a subgroup of HCC patients. There are currently a number of antiangiogenic agents targeting the VEGF/VEGFR axis, which can be broadly categorized as monoclonal antibodies and tyrosine kinase inhibitors. These agents are being evaluated in a number of gastrointestinal cancers.