Lung cancer is the leading cause of cancer-related mortality in the United States. Patients with advanced disease have a median survival of approximately 10 months when treated with standard platinum-based therapy. Improvements in our understanding of cancer biology have led to the development of novel agents that more precisely affect the target of interest, allowing for a more rational approach to clinical trial design. Angiogenesis, the growth of new vessels from pre-existing vessels, is a fundamental step in tumor growth and progression. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. A large randomized trial demonstrated an improvement in overall survival when bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), was combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Small molecule inhibitors targeting both the VEGF receptor (VEGFR) and the tyrosine kinase receptor have also shown promise when combined with standard chemotherapy, but their role in the treatment of patients with NSCLC remains to be determined. This paper reviews clinical trials that have incorporated antiangiogenic agents in the treatment of patients with NSCLC.