Lung cancer is one of the leading causes of death in Europe and the USA. A relatively good prognosis is limited to those patients in whom the tumor is detected at an early stage. As clinical symptoms of lung cancer are a late finding in the natural course of the disease, most of the patients are diagnosed at an advanced tumor stage when palliative care remains the only therapeutic option. For this reason, early diagnosis of lung cancer might save lives. The National Lung Screening Trial (NLST), in the U. S. A., provided evidence that screening with low-dose CT (LD-CT) is able to reduce lung cancer mortality by 20.0 %. The encouraging results of the NLST, however, could not be confirmed by the preliminary results of ongoing European trials. Even if the European trials are able to confirm a reduction in lung cancer mortality by LD-CT, a number of important questions must be answered before the implementation of nationwide screening programs. First of all, the population that might benefit from CT lung cancer screening has to be defined precisely. Furthermore, guidelines have to be established about how to manage screening participants with detected lung nodules, as the vast majority of these pulmonary nodules will prove to be benign. This review article summarizes the results of the NLST and the initial data from the European screening trials, and will discuss some of the major open questions in lung cancer screening with CT.