The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine at the annual international conference. The 2021 Pulmonary Core Curriculum focuses on lung cancer and include risks and prevention, screening, nodules, therapeutics and associated pulmonary toxicities, and malignant pleural effusions. Although tobacco smoking remains the primary risk factor for developing lung cancer, exposure to other environmental and occupational substances, including asbestos, radon, and burned biomass, contribute to the global burden of disease. Randomized studies have demonstrated that routine screening of high-risk smokers with low-dose chest computed tomography results in detection at an earlier stage and reduction in lung cancer mortality. On the basis of these trials and other lung cancer risk tools, screening recommendations have been developed. When evaluating lung nodules, clinical and radiographic features are used to estimate the probability of cancer. Management guidelines take into account the nodule size and cancer risk estimates to provide recommendations at evaluation. Newer lung cancer therapies, including immune checkpoint inhibitors and molecular therapies, cause pulmonary toxicity more frequently than conventional chemotherapy. Treatment-related toxicity should be suspected in patients receiving these medications who present with respiratory symptoms. Evaluation is aimed at excluding other etiologies, and treatment is based on the severity of symptoms. Malignant pleural effusions can be debilitating. The diagnosis is made by using simple pleural drainage and/or pleural biopsies. Management depends on the clinical scenario and the patient’s preferences and includes the use of serial thoracentesis, a tunneled pleural catheter, or pleurodesis.