Abstract: Non-small cell lung cancer (NSCLC) is currently the leading cause of cancer-related deaths worldwide. Angiogenesis, the formation of new vasculature, is a complex and strictly regulated process that promotes metastasis and disease progression in lung cancer and other malignancies. Anti-angiogenic therapy is an anti-cancer strategy that targets the new vessels. Most anti-cancer agents used in the clinic include cytotoxic drugs, which target all rapidly dividing cells, resulting in severe adverse effects. These effects include immunosuppression, intestinal problems, and hair loss. By contrast, anti-angiogenic agents theoretically exhibit fewer side effects because angiogenesis rarely occurs in healthy adults, except in the uterine endometrium. Various angiogenic factors may contribute to the regulation of angiogenesis in the individual tumor; thus, the proper selection of patients who may benefit from a specific therapy is important, considering the increasing number of clinically tested agents. This study provides an overview of angiogenic molecules currently being investigated as prognostic and predictive biomarkers in NSCLC. Clinical examples are presented to show the rationales for investigating various biomarkers of pre-clinical studies.