Cigarette smoking has been causally linked several diseases, primarily lung cancer and chronic obstructive lung disease (COPD). The diagnosis of COPD currently involves an assessment of smoking and/or occupational exposures, a history of cough, sputum and dyspnea and spirometric measures of airflow obstruction and since spirometric measures take long follow up times to detect significant changes, surrogate measures of outcome capable of predicting long-term health changes have been sought for. These include biomarkers of oxidative stress, inflammation and tissue damage in sputum, bronchoalveolar lavage, exhaled breath and serum. Published biomarker studies have not always accurately compared patients with COPD with age-matched cigarette smokers and non-smoking normal subjects without significant airflow limitation, also comparable for other exposures. Consequently, the interpretation of biomarker association studies is somewhat difficult. The purpose of this narrative review is to summarize publications reporting cellular, soluble or volatile marker of obstructive lung disease in populations of healthy non-smokers and healthy smokers, in order to determine whether the biomarkers examined could be specifically associated with exposure to tobacco smoke rather than with inflammation and airway hyper-reactivity. As induced sputum has been the most widely used investigative tool, this review has been aimed at assessing induced sputum biomarkers, referring to lung biopsy, bronchoalveolar lavage and exhaled breath markers as supporting evidence for biomarkers associations identified with induced sputum studies.