Despite major advances in the treatment and management of lung cancer, most patients with lung cancer eventually die of this disease. Because conventional therapies have failed to make a major impact on survival, newer approaches are necessary in the battle against lung cancer. Better understanding of molecular biology of several tumors has led to novel targeted therapeutic approaches with potential utility in cancer treatment in general and lung cancer in particular. In addition to smoking cessation, targeting individuals at high risk by use of early detection or aiming at reversal of premalignant lesions seem like attractive strategies. In light of the noted improvement in molecular diagnostic tools and targeted therapies, the question of chemoprevention in the context of early detection deserves a closer look. In this article, we review what has been achieved in the area of chemoprevention and discuss possible prospects that may help reduce lung cancer mortality in the context of early detection.