Currently, nonsmall-cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Angiogenesis, the formation of new vasculature, is a complex and tightly regulated process that promotes metastasis and disease progression in lung cancer and other malignancies. Developmental antiangiogenic agents have shown activity in NSCLC, and bevacizumab, an antiangiogenic monoclonal antibody, is approved for the treatment of patients with advanced disease. However, predictive biomarkers are needed to guide the administration of antiangiogenic agents. It is possible that angiogenic molecules could accurately predict patient response to targeted antiangiogenic therapies, which would allow individualized and perhaps more effective treatment. Angiogenic signaling molecules may also have value as prognostic indicators, which may be useful for the management of NSCLC. Here the author provides an overview of angiogenic molecules currently being investigated as prognostic biomarkers in NSCLC and discusses their potential to guide treatment choices. Cancer 2011;. © 2011 American Cancer Society.