The addition of oxaliplatin and irinotecan to the armamentarium for the treatment of colorectal cancer (CRC) has resulted in significant improvements in response rates and survival. Targeted therapies directed at the epidermal growth factor pathway and the vascular endothelial growth factor pathway are beginning to play a role in the treatment of CRC. Bevacizumab is a monoclonal antibody that has been evaluated in randomized studies. In a randomized phase II study, the combination of 5-fluorouracil/leucovorin (5-FU/LV) was compared with 5-FU/LV plus bevacizumab, and a randomized phase III trial evaluated the addition of bevacizumab to the irinotecan/5-FU/LV (IFL) regimen compared with IFL plus placebo. The results of these studies will be reviewed in detail. The role of bevacizumab with other first-line combinations in the treatment of patients with advanced CRC is being evaluated in ongoing clinical trials. Additionally, the activity of bevacizumab is being evaluated for use in the second-line treatment setting for patients with CRC.