Angiogenesis is essential for tumor growth and metastasis and is a promising target in the search for new anti-neoplastic agents. Angiogenesis is a tightly regulated process dependent on the complex interplay between inhibitory and stimulatory angiogenic factors. Vascular endothelial growth factor is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against vascular endothelial growth factor, has shown initial preclinical and clinical activity. This review will outline the conceptual basis of anti-angiogenic therapy, discuss the critical role of vascular endothelial growth factor, and summarize the available data on the use of bevacizumab in colorectal cancer.