There is increased awareness of smoking-related lung diseases other than lung cancer and chronic obstructive pulmonary disease. Concurrently, there is general acceptance that there is difficulty in establishing a specific diagnosis of smoking-related interstitial lung disease (ILD), as many patients may not undergo biopsy to facilitate a specific histopathologic diagnosis. Cases that do proceed to biopsy may demonstrate multiple abnormalities, and histologic overlap between different disease processes may confound the picture. This review outlines the key aspects of smoking-related lung disease, including entities secondary to smoking-related lung inflammation such as respiratory bronchiolitis-ILD, desquamative idiopathic pneumonia, and pulmonary Langerhans cell histiocytosis, as well as chronic fibrosing lung diseases strongly associated with cigarette smoke including idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, nonspecific interstitial pneumonia, and rheumatoid arthritis-ILD. The focus will be on incorporation of clinical findings, key pulmonary function testing parameters, high-resolution computer tomography (HRCT) findings, and pathologic correlates in refining the differential diagnosis and differentiating between the various entities.