The statistics on lung cancer form a powerful argument to develop new methods to control this most deadly form of cancer. Chemoprevention is one of these new approaches. Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer. At the same time it has become increasingly clear that dietary and genetically determined factors play an important role in modulating the individual susceptibility and are linked to the chemoprevention approach. In spite of many positive pre-clinical observations, most of the experiences with potential chemopreventive agents such as retinoids and antioxidants in individuals at risk for lung cancer have been negative so far. Moreover, beta-carotene was associated with an increased lung cancer incidence in two large randomized studies, most likely due to negative interaction with cigarette smoke. The recent progress in diagnostic techniques and molecular biology has led to a new paradigm for chemoprevention and there is considerable optimism regarding the potential of new molecules and antibodies that target specific cellular receptors or mutations. This article reviews the lung cancer chemoprevention efforts of the last two decades and also gives prospects for the next coming years.