OVERVIEW: The results of the National Lung Screening Trial (NLST) have provided the medical community and American public with considerable optimism about the potential to reduce lung cancer mortality with imaging-based screening. Designed as a randomized trial, the NLST has provided the first evidence of screening benefit by showing a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality with low dose helical computed tomography (LDCT) screening relative to chest X-ray. The major harms of LDCT screening include the potential for radiation-induced carcinogenesis; high false-positivity rates in individuals without lung cancer, and overdiagnosis. Following the results of the NLST, the National Comprehensive Cancer Network (NCCN) published the first of multiple lung cancer screening guidelines under development by major medical organizations. These recommendations amalgamated screening cohorts, practices, interpretations, and diagnostic follow-up based on the NLST and other published studies to provide guidance for the implementation of LDCT screening. There are major areas of opportunity to optimize implementation. These include standardizing practices in the screening setting, optimizing risk profiles for screening and for managing diagnostic evaluation in individuals with indeterminate nodules, developing interdisciplinary screening programs in conjunction with smoking cessation, and approaching all stakeholders systematically to ensure the broadest education and dissemination of screening benefits relative to risks. The incorporation of validated biomarkers of risk and preclinical lung cancer can substantially enhance the effectiveness screening programs.