Lung cancer screening with CT remains controversial. Lung cancer is the leading cause of cancer death. To date, no screening test has been demonstrated to reduce mortality. Given the large population of adult cigarette smokers and former smokers worldwide, there is a large population at risk for lung cancer. While a lot has been learned from prospective single-arm cohort studies about the feasibility of performing annual CT to screen for lung cancer, many questions have also been raised. While we know that screening for lung cancer with CT detects many small nodules, with up to half the subjects having a positive baseline screen, and up to 75% of subjects having a positive screen at least once if screened annually for 5 years, the great majority of these nodules exhibit benign biologic behavior. The innumerable small nodules detected with screening CT, and diagnostic chest CT in general, present a daily clinical challenge, and result in extensive medical resource utilization and additional radiation exposure. Algorithms for how and when to follow small nodules detected on CT are in evolution. Ongoing studies are designed to determine if lung cancer screening with CT reduces lung cancer mortality.