Lung cancer continues to be the most lethal of human tumors and is expected to account for > 160,000 deaths in 2004.1 This high mortality has been attributed to the late stage of the disease at detection and to aggressive biological behavior. Because of this aggressive behavior, there is a relatively short window of opportunity in which to effectively treat the disease. However, if the preinvasive changes in progenitor cells that lead to carcinoma are recognized as part of the process of malignant transformation, then the window of opportunity for effective intervention is considerably widened. In such a paradigm, premalignancy is regarded as the disease, and carcinoma as the end point. The objective of this article is to review the evidence for the existence of premalignant lesions in the lower airways, to determine who develops the lesions and how to find them, and to describe the molecular and cellular properties of those lesions.