Lung cancer remains the leading cause of cancer-related deaths in southern Africa. Early trials of chest radiograph-based screening in males at high risk for lung cancer found no mortality benefit of a radiograph alone, or a radiograph plus sputum cytology screening strategy. Large prospective studies, including the National Lung Screening Trial, have shown an all-cause mortality benefit when low-dose computed tomography (LDCT) was used as a screening modality in patients that are at high risk of developing lung cancer. The South African Thoracic Society, based on these findings, and those from several international guidelines, recommend that annual LDCT should be offered to patients between 55-74 years of age who are current or former smokers (having quit within the preceding 15 years), with at least a 30-pack year smoking history and with no history of lung cancer. Patients should be in general good health, fit for surgery, and willing to undergo further investigations if deemed necessary. Given the high local prevalence of tuberculosis (TB) infection and post-TB lung disease, which can radiographically mimic lung cancer, a conservative threshold (nodule size ≥6 mm) should be used to determine whether the baseline LDCT screen is positive (thus nodules <6 mm require no action until the next annual screen). If a non-calcified, solid or partly solid nodule is ≥6 mm, but <10 mm with no malignant features (e.g., distinct spiculated margins), the LDCT should be repeated in 6 months. If a solid nodule or the largest component of a non-solid nodule is ≥10 or ≥6 mm and enlarging or with additional malignant features present, definitive action to exclude lung cancer is warranted. Patients should be screened annually until 15 years have elapsed from date of smoking cessation, they turn 80, become unfit for a curative operation or significant changes are observed.