Cigarette smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD) and lung cancer, but only a part of smoking subjects develop these respiratory pathologies. Therefore, it is necessary to find sensible parameters to detect early lung alterations due to chronic tobacco smoke exposure. Long-term cigarette smoking is associated with a persistent inflammatory response in the lung that leads to tissue injury and dysfunction. Bronchoscopy and bronchial biopsies are the gold standard techniques for assessing pulmonary inflammation, but are invasive and not routinely used. Cellular analysis of induced sputum and measurement of fraction of exhaled nitric oxide (FENO) are validated non-invasive techniques for assessing respiratory inflammation. Measurement of biomolecules in sputum supernatants and exhaled breath condensate (EBC) are used as a research tool, but require standardization of procedures and, generally, analytical validation. Electronic nose differentiates healthy smokers from healthy nonsmokers based on breath volatile organic compounds (VOC) patterns. These techniques are potentially useful for identifying biomarkers of pulmonary inflammation and oxidative stress. Induced sputum, FENO, EBC and electronic nose are suitable for longitudinal sampling, thereby facilitating monitoring of lung damage process. This approach could enable an early identification of subgroups of healthy smokers at higher risk for tobacco-induced lung damage and prompt planning of secondary prevention strategies.