There is an unmet need in the diagnosis, phenotyping, and staging of COPD that could potentially be fulfilled by a validated molecular biomarker. Many promising candidates have been investigated, and some have been shown to be useful in certain situations. However, to date there is no outstanding disease-specific biomarker for widespread clinical application for patients in the stable state. Given the functional, social, and financial importance of exacerbations of COPD, it would be very useful to be able to employ a biomarker to aid optimal treatment and predict clinical outcome from the acute episode. Although serum C-reactive protein (CRP) is not specific to COPD, its use as a molecular biomarker in the stable state and at exacerbation has been studied extensively, and it remains the most commonly measured molecular biomarker in routine secondary care practice. Utilizing biomarkers in combinations may ultimately prove more useful. Airway-derived biomarkers and their relationships with outcome measures require further longitudinal study as well as refinement of sampling techniques to make them more broadly applicable. There is substantial ongoing investigation of many biomarkers that we are hopeful will advance the field for the benefit of our patients.