Low-dose CT screening for lung cancer is a complex and controversial topic. This article reviews the history of lung cancer screening trials and addresses the principles and confounding biases associated with screening. Chest radiography was initially used for lung cancer screening in the 1970s. In the mid-1990s helical single-detector CT came into use, followed by helical multidetector CT, the current method of screening. Results from prevalence studies and a few single-arm incidence studies have raised concerns about overdiagnosis and the high rate of nodule detection. Follow-up studies and further investigation are needed. To this end, a randomized, controlled trial sponsored by the National Cancer Institute is underway to evaluate disease-specific mortality.