Biomarkers that focus on lung cancer risk assessment, detection, prognosis, diagnosis, and personalized treatment are in various stages of development. This article provides an overview of lung cancer biomarker development, focusing on clinical utility and highlighting 2 unmet clinical needs: selection of high-risk patients for lung cancer screening and differentiation of early lung cancer from benign pulmonary nodules. The authors highlight biomarkers under development and those lung cancer screening and nodule management biomarkers post-clinical validation. Finally, trends in lung cancer biomarker development that may improve accuracy and accelerate implementation in practice are discussed.