Lung cancer remains the most common cause of cancer death in the United States and worldwide. About 80~90% of cases are smoking-related and smoking cessation programs are of great importance in reducing lung cancer risk. However, the lifetime risk for lung cancer remains elevated even in ex-smokers. Chemoprevention holds the promise to further reduce this risk and thus to decrease lung cancer incidence and mortality. Over the last decades, most chemoprevention trials for lung cancer have yielded negative outcomes. Population-based studies suggest that high intake of certain foods such as soy, red wine or green vegetables may be associated with decreased cancer risk. Because of these observations and their general safety, a plethora of natural compounds is currently being studied for the chemoprevention of cancer. In this review we discuss promising in vitro and in vivo data of novel natural compounds, their interference with molecular mechanisms responsible for lung cancer development and potential implications for their further preclinical and clinical investigation.