Lung cancer is the leading cause of cancer-related death in the United States. Despite the availability of several cytotoxic and a few molecularly targeted agents, the outlook for patients with advanced non-small cell lung cancer continues to be dismal. Novel approaches are desperately needed. The insulin-like growth factor (IGF) pathway plays an important role in a number of human malignancies contributing to unregulated cell proliferation. The IGF pathway has several targets for therapeutic intervention.