Abstract:Lung cancer is the commonest cause of cancer deaths worldwide, and its mortality can be reduced significantly by performing early diagnosis and screening. Since the 1960s, driven by the pressing needs to accurately and effectively interpret the massive volume of chest images generated daily, computer-assisted diagnosis of pulmonary nodule has opened up new opportunities to relax the limitation from physicians subjectivity, experiences and fatigue. It has been witnessed that significant and remarkable advances have been achieved since the 1980s, and consistent endeavors have been exerted to deal with the grand challenges on how to accurately detect the pulmonary nodules with high sensitivity at low false-positives rate as well as on how to precisely differentiate between benign and malignant nodules. The main goal of this investigation is to provide a comprehensive state-of-the-art review of the computer-assisted nodules detection and benign-malignant classification techniques developed over three decades, which have evolved from the complicated ad hoc analysis pipeline of conventional approaches to the simplified seamlessly integrated deep learning techniques. This review also identifies challenges and highlights opportunities for future work in learning models, learning algorithms and enhancement schemes for bridging current state to future prospect and satisfying future demand. As far as the authors know, it is the first review of the literature of the past thirty years development in computer-assisted diagnosis of lung nodules. We acknowledge the value of potential multidisciplinary researches that will make the computer-assisted diagnosis of pulmonary nodules enter into the main stream of clinical medicine, and raise the state-of-the-art clinical applications as well as increase both welfares of physicians and patients.