Recently, there has been widespread interest in the use of non-invasive methods for the assessment of airway inflammation in a variety of lung diseases including chronic obstructive pulmonary disease (COPD). Sputum induction is a semi-invasive technique the value of which is not restricted to sputum cell counts, as inflammatory mediators can also be measured in the supernatants. However, none of the measurable biomarkers in induced sputum is considered applicable in clinical practice. Despite the predominating sputum neutrophilia, there is increasing evidence that the presence of sputum eosinophilia predicts an objective response to steroid treatment in patients with COPD. The commonly used Exhaled Breath Condensate (EBC) methodologies in COPD patients have considerable variability due to technical issues concerning both sample collection and analysis. Despite the above limitations, biomarkers mainly related to neutrophil derived products and oxidative stress, have been assessed for disease monitoring and response to pharmacological treatment. Endogenous airway acidification, as assessed by EBC pH, represents a measurable marker associated with oxidative stress and sputum neutrophilia. The fraction of exhaled nitric oxide (FeNO) is the most extensively studied exhaled biomarker and increased levels of FeNO have been widely documented in patients with asthma. FeNO measurement in COPD is of limited value due to smoking effect. However, increased values of FeNO have been found in COPD patients with sputum eosinophila. Moreover, measuring FeNO in different exhalation rates may reestablish its value in COPD. Despite the limited use of non-invasive methods, the future direction is a challenge towards new biomarkers or a combination of them that will assist us to move from the research laboratory to daily clinical practice.