Sustained angiogenesis is one of the hallmarks of carcinogenesis. Vascular endothelial growth factor (VEGF) is a crucial molecule mediating proangiogenic signals against which a number of therapeutic approaches have been designed, such as monoclonal antibodies, small-molecule receptor kinase inhibitors, and nucleic acid inhibitors. The VEGF signaling pathway as a target in lung cancer therapy was validated by a randomized phase III study of platinum agent-based combination chemotherapy with or without bevacizumab, a recombinant humanized monoclonal antibody against VEGF-A, in first-line, nonsquamous, metastatic non-small-cell lung cancer. This trial demonstrated an improvement in overall survival among patients who received bevacizumab in comparison with those who received carboplatin and paclitaxel alone. In this review, we will discuss various aspects of this pivotal trial and highlight issues relevant to angiogenesis inhibition in the treatment of non-small-cell lung cancer.