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Thoracic imaging plays an essential role in understanding and diagnosing chest disease. It has traditionally relied on conventional anatomic and morphologic imaging, but as technology evolves, novel diagnostic strategies have the potential to improve accuracy. This includes incorporation of biomarkers, which are an objective measure of a biological or pathological process. Biomarkers can be used in multiple different scenarios, and may complement current imaging studies, particularly in establishing a diagnosis, determining prognosis or predicting response to therapy. However, it is important to develop and validate clinically relevant biomarkers. This is a complex, multidisciplinary subject that requires knowledge of the clinical problem, an understanding of the technology and pathology, and significant resources. Ultimately, integration of biomarkers into patient evaluation must be cost effective and improve outcomes. This article will describe the potential roles and limitations of biomarkers in thoracic diseases.