Lung cancer is the leading cause of cancer death in the United States. In 2007, it is estimated that 160,390 lung cancer deaths will occur in the US, representing 29% of all cancer deaths (1). Roughly 87% of lung cancers are attributed to cigarette smoking (2). Although cancer risk is attenuated by smoking cessation, the risk is not eliminated, and lung cancer now occurs with equal frequency in current and former smokers (3). Moreover, other factors clearly influence risk, including age; family history; chronic obstructive pulmonary disease; pulmonary fibrosis; and exposures to environmental radon, asbestos, and certain other occupational agents (4). Realistically, lung cancer will likely remain at epidemic proportions for decades to come.Non-small cell lung cancer (NSCLC), which accounts for 75-80% of all lung cancers, is typically diagnosed when disease is locally advanced or there are systemic metastases (5), explaining the dismal overall five-year survival of 15% (6). In contrast, the five-year survival of individuals with surgically resected, early stage NSCLC approaches 75% (6,7). These differences have fueled the impetus to find a screening test that can detect NSCLC in its early preclinical stages, when surgical resection is most likely to prolong life and potentially reduce lung cancer mortality. Although earlier randomized controlled trials of lung cancer screening using chest radiography and sputum cytology failed to show reduced lung cancer mortality, computed tomography (CT) is a much more sensitive test for detecting small lung nodules, and has generated considerable enthusiasm as a potential contemporary screening tool for lung cancer.