Lung cancer continues to be one of the main causes of cancer death in Europe. Low-dose computed tomography (LDCT) has shown high potential for screening of lung cancer in smokers, most recently in two European trials. The aim of this review was to assess lung cancer screening of smokers by LDCT with respect to clinical effectiveness, radiological procedures, quality of life, and changes in smoking behavior. We searched electronic databases in April 2020 for publications of randomized controlled trials (RCT) reporting on lung cancer and overall mortality, lung cancer morbidity, and harms of LDCT screening. A meta-analysis was performed to estimate effects on mortality. Forty-three publications on 10 RCTs were included. The meta-analysis of eight studies showed a statistically significant relative reduction of lung cancer mortality of 12% in the screening group (risk ratio = 0.88; 95% CI: 0.79–0.97). Between 4% and 24% of screening-LDCT scans were classified as positive, and 84–96% of them turned out to be false positive. The risk of overdiagnosis was estimated between 19% and 69% of diagnosed lung cancers. Lung cancer screening can reduce disease-specific mortality in (former) smokers when stringent requirements and quality standards for performance are met.