Cigarette smoke, a toxic collection of more than 4000 chemicals generated from combustion of tobacco plant leaves, is known to cause several respiratory ailments, including chronic bronchitis, emphysema and lung cancer, and is associated with an increase in respiratory infections. In addition, cigarette smoking is considered a principal aetiological factor responsible for the development of certain diffuse interstitial and bronchiolar lung diseases, namely respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP) and adult pulmonary Langerhans' cell histiocytosis (PLCH). Although not exclusively seen in cigarette smokers, substantial clinical and epidemiological data support a central role for smoking as the primary causative agent of most RB-ILD, DIP and PLCH. Additional evidence in support of cigarette smoke as a primary aetiological agent in RB-ILD, DIP and PLCH is the observation that smoking cessation may lead to disease improvement, while recurrence of these disorders has been observed to occur in the transplanted lung upon re-exposure to tobacco smoke. Furthermore, histopathological changes of respiratory bronchiolitis, DIP and PLCH (with or without co-existent emphysema) may be found on lung biopsy in the same individual, implicating smoking as a common inciting agent of these diverse lesions. Recent studies also suggest a role for cigarette smoking as a potential co-factor in the development of acute eosinophilic pneumonia, usual interstitial pneumonia and rheumatoid arthritis-associated interstitial lung disease. In the current review, we propose a novel classification that takes into account the complex relationship between cigarette smoking and diffuse lung diseases. Investigation on the role of smoking as a potential causative factor or modifier of these diverse diffuse lung diseases is important, as smoking cessation utilizing state-of-the-art tobacco cessation efforts should be a central part of therapy, while pharmacotherapy with corticosteroids or other immune modifying agents should be reserved for selected patients.