Chronic obstructive pulmonary disease (COPD) is defined as airflow limitation that is not fully reversible, usually progressive and associated with an abnormal inflammatory response to noxious particles or gases. By the time COPD has progressed to the point of clinical symptoms, over half of lung function may have been lost. This review will first describe studies that have examined the feasibility and yield of early detection of COPD using spirometry as a gold standard. Next, we will review existing studies that have examined the effects of pharmacotherapy on early (mild-to-moderate) COPD, specifically focusing on studies that have attempted to alter the natural history of disease. Finally, we will briefly discuss studies that have tested the effects of various pharmacologic interventions on biomarkers felt to be relevant to disease pathogenesis. Discovery of effective pharmacotherapy that can prevent disease progression in early-stage COPD has enormous public-health implications, given the current global burden of disease and the proportion of individuals at risk - aging current and former smokers.